Skeletal muscle laminin and MDC1A: pathogenesis and treatment strategies
© Gawlik and Durbeej; licensee BioMed Central Ltd. 2011
Received: 6 December 2010
Accepted: 1 March 2011
Published: 1 March 2011
Laminin-211 is a cell-adhesion molecule that is strongly expressed in the basement membrane of skeletal muscle. By binding to the cell surface receptors dystroglycan and integrin α7β1, laminin-211 is believed to protect the muscle fiber from damage under the constant stress of contractions, and to influence signal transmission events. The importance of laminin-211 in skeletal muscle is evident from merosin-deficient congenital muscular dystrophy type 1A (MDC1A), in which absence of the α2 chain of laminin-211 leads to skeletal muscle dysfunction. MDC1A is the commonest form of congenital muscular dystrophy in the European population. Severe hypotonia, progressive muscle weakness and wasting, joint contractures and consequent impeded motion characterize this incurable disorder, which causes great difficulty in daily life and often leads to premature death. Mice with laminin α2 chain deficiency have analogous phenotypes, and are reliable models for studies of disease mechanisms and potential therapeutic approaches. In this review, we introduce laminin-211 and describe its structure, expression pattern in developing and adult muscle and its receptor interactions. We will also discuss the molecular pathogenesis of MDC1A and advances toward the development of treatment.
Laminin α2 chain gene and protein
The LAMA2 gene is located on chromosome 6q22-23 in humans and on chromosome 10 in mice [10–12]. The gene is composed of 65 exons that encode a protein with a predicted molecular mass of 390 kDa. However, it is cleaved by a furin-like convertase into a 300 kDa N-terminal segment and a 80 kDa C-terminal segment, which remain non-covalently associated [13–15]. Whether this proteolytic processing has functional consequences in muscle in vivo is not known. The laminin α2 chain has a similar domain organization to that of the other laminin chains, with several globular and rod-like regions. Domains LN, L4a and L4b form globular structures separated by rod-like spacers of LE domains (epidermal growth factor-like repeats), followed by a coiled-coil domain, and finally, the C-terminal end is composed of five homologous laminin globular (LG) domains (LG1 to LG5) (Figure 1) . Key biologic activities have been mapped to several of these domains. The LN domain is essential for laminin polymerization into supramolecular networks and consequently for incorporation into basement membranes , and mutations in this domain reduce the ability of polymer formation . The coiled-coil domain is involved in the formation of laminin heterotrimers, and the laminin α2 chain can assemble with the β1, γ1, β2 and γ3 chains to form laminins 211, 221 and 213 . The laminin α2 LG domains at the C-terminus bind cellular receptors (dystroglycan and integrin α7β1) [15, 18], and such interactions are required for adhesion, basement-membrane assembly and downstream signaling events [19, 20].
Laminin-211 and other laminins in developing muscle
Myogenesis is a complex multistep process, but it has been found that muscle morphogenesis is strongly guided by ECM cues . There is robust evidence that laminins are important for synaptogenesis [22–26], but their precise function in myogenesis is still not known. Each immature murine somite is surrounded by a laminin-111-rich basement membrane . While entering the myotome during somite differentiation, muscle progenitors begin to form the myotomal basement membrane that separates the myotome and sclerotome , and laminin-111 seems to be fundamental for the initiation of its assembly, at least in mice . After the initial myogenic events, formation of primary and secondary myotubes takes place. Basement-membrane remodeling and differential expression of laminin subunits is tightly correlated with these events. During the first fusion events in mice at embryonic day (E)11, laminin-211 and laminin-511 are the major heterotrimers of the newly formed basement membrane (the laminin α1 chain is still present at E11.5, but it is largely restricted to the ends of myotubes) . Just before the fusion of secondary myotubes (at E14), expression of the laminin α4 chain increases dramatically, and it is deposited throughout the secondary myotube basement membrane by E15 . In developing human muscle, the laminin α2 chain is present from around the seventh week of gestation, reaching maximum expression levels at week 21 [30, 31], and the laminin α4 chain is strongly expressed at week 16 . Additionally, the laminin α5 subunit was shown to be a major laminin α chain during myogenesis in humans, whereas the laminin α1 subunit was detected only in the developing myotendinous junction (MTJ) [31, 33]. It is noteworthy that the laminin composition is also modified during development of specialized muscle sites, such as the neuromuscular junction (NMJ) and the MTJ [9, 31, 34].
Further changes om the laminin array in muscle basement membrane occur perinatally both in human and mouse as myotubes mature into myofibers. The levels of laminin α4 and α5 subunits markedly decrease at birth and are not detectable at the sarcolemma by the end of the first postnatal week [9, 32, 35]. Thus, the laminin α2 subunit is the only laminin α chain expressed in the extrasynaptic basement membrane. Interestingly, in vitro studies with myogenic cell lines found that both the laminin α1 and α2 chains possess myogenic properties, performing both shared and specific tasks in myogenesis [36, 37].
Although several laminins are expressed in a distinct manner during myogenesis, none of the laminin α chains seems to be essential for this event [23, 38, 39]. Myogenesis occurs normally in patients and mice lacking laminin α2 subunit [11, 12, 40–43], even though myofibers are smaller at birth in patients with MDC1A [40, 41]. It is possible that laminin α4 and/or α5 could compensate for absence of the laminin α2 chain in developing muscle, and studies of muscles devoid of several α chains would be therefore be interesting. Laminins containing the α2 chain are instead crucial in adult muscle, and this topic will be discussed in more detail in later sections.
Laminin-211 and other laminins in mature muscle
Laminin-211 in the sarcolemmal basement membrane is extremely important for maintenance and stabilization of differentiated muscle [37, 50], and absence of the laminin α2 chain leads to muscular dystrophy in humans and mice [10–12, 40–43]. Subtle NMJ defects have also been reported in laminin α2 chain-deficient mice , but it is possible that these arise from muscle abnormalities caused by the dystrophic process. The laminin α4 and β2 chains, by contrast, have important roles in the NMJ. Mice devoid of the laminin α4 and β2 chainshave abnormal neuromuscular (synapses) [22, 23, 26], and laminin β2 chain deficiency in humans (Pierson syndrome) is characterized by muscular and neurologic defects in addition to kidney failure .
Laminin receptors in skeletal muscle
Integrin α7β1 is the second transmembrane unit that links laminin-211 to the cytoskeleton [58–60] and binding occurs through the laminin α2 LG1 to3 domain with involvement of the coiled-coil domain [14, 15]. However, the adaptor molecules that connect integrin α7β1 to the cytoskeleton remain to be identified , although talin  and integrin-linked kinase  are likely candidates. We also recently identified a novel integrin α7β1 interacting protein (Cib2), whose expression in muscle is dependent on the presence of the laminin α2 chain .
The significance of the laminin receptors for normal muscle function is emphasized by the fact that mutations in DGC components and post-translational defects in dystroglycan processing and mutations in the integrin α7 gene causes various forms of muscular dystrophy and myopathy [65, 66]. Hence, there is strong evidence that both receptors contribute to linking laminin-211 to the cytoskeleton and mediate the effects of laminin-211 on muscle integrity and function. It has been shown that the two systems act synergistically [67, 68], but separate roles have also been delineated [69, 70]. Both dystroglycan and integrin α7β1 contribute to force production, but only dystroglycan is involved in anchoring the basement membrane to the sarcolemma . Furthermore, different muscles may have different requirements for the laminin-dystroglycan interaction as it may not be crucial in diaphragm but important in limb muscle . Nevertheless, many of the downstream events of the laminin-211-receptor interaction remain to be elucidated. Several signaling pathways may be affected, but the importance of each of those pathways in skeletal muscle is not obvious [71–76].
Finally, it should be noted that laminin-211 also binds other cell-surface receptors, although dystroglycan and integrin α7β1 may be considered as the major laminin-211 receptors in skeletal muscle. These other receptors include the syndecans and sulfated glycolipids [18, 77]. Interestingly, sulfatides have been proposed to anchor laminin-211 by binding to its LG domains to initiate basement-membrane assembly and to engage the activation of receptors (dystroglycan and β1 integrins), at least in Schwann cells .
Congenital muscular dystrophy type 1A
Mouse models for laminin α2 chain deficiency
Mouse models for laminin α2 chain deficiency.
Unknown spontaneous mutation/reduced expression of seemingly normal α2 chain
Lethal within 6 months of age. Moderate muscular dystrophy; peripheral neuropathy; defective central nervous system myelination; hearing loss; aberrant thymocyte development
dy 2J /dy 2J
Spontaneous mutation in LN domaina/slightly reduced expression of truncated α2 chain devoid of LN domain
Normal lifespan. Mild muscular dystrophy; peripheral neuropathy
dy W /dy W
Knock- out/severely reduced expression of truncated α2 chain devoid of LN domain
Lethal at 10 to 15 weeks of age. Severe muscular dystrophy; peripheral neuropathy
dy 3K /dy 3K
Lethal at 4 weeks of age. Severe muscular dystrophy; peripheral neuropathy; impaired spermatogenesis; defective odontoblast differentiation
dy nmj417 /dy nmf417
N-ethyl-N-nitrosourea-induced point mutation in LN domain/normal levels
Normal lifespan. Mild muscular dystrophy; peripheral neuropathy
dy Pas /dy Pas (now extinct)
Spontaneous retrotransposal insertion/severe deficiency
Died at 13 weeks of age. Severe muscular dystrophy; peripheral neuropathy
Although it can be debated whether mice are reliable as preclinical models for human disease, analyses of the various laminin α2 chain-deficient mouse models have led to a significant improvement in our understanding of development of MDC1A. More importantly, they have been valuable tools for the development of novel therapeutic approaches for laminin α2 chain deficiency.
Pathogenesis of MDC1A muscle
At the molecular level, absence of the laminin α2 chain affects the expression and localization of several other laminin chains and cell-surface receptors. In particular, expression of the laminin β2 chain is severely reduced from the sarcolemmal basement membranes in laminin α2 chain-deficient muscle . Conversely, laminin α4 (and α5 chain to some extent) is increased at this site [9, 98]. However, it does not seem to compensate for the absence of the laminin α2 chain, presumably because the laminin α4 chain cannot bind α-dystroglycan , or possibly because that the laminin α4 chain is not upregulated in sufficient amounts. In extraocular muscles, which have a number of differences from other skeletal muscles, the laminin α4 chain is strongly expressed in the basement membrane adjoining the sarcolemma, and its expression is further enhanced in the extraocular muscle of dy 3K /dy 3K animals. Interestingly, laminin α2 chain-deficient extraocular muscles are spared from dystrophic changes, and it has been hypothesized that binding of the laminin α4 chain to integrin α7β1 may protect the extraocular muscles from damage [100, 101].
Changes in the expression of laminin-211 receptors might also contribute to the pathology of MDC1A. A dramatic decrease of integrin α7 subunit in muscle from laminin α2 chain-deficient patients and mice [60, 102, 103], and a striking impairment of its deposition at the sarcolemma , has been noted, suggesting that integrin α7β1 signaling is abolished. By contrast, expression of β-dystroglycan at the sarcolemma, is upregulated in laminin α2 chain-deficient mouse muscle [104, 105]. However, conflicting data have been reported on α-dystroglycan expression, with its production either not found to be significantly affected by laminin α2 chain deficiency [60, 103] or shown to be moderately increased . Moll et al. and Jimenez-Mallebrera et al. reported severe reduction of α-dystroglycan core protein [105, 106]. The precise physiological outcomes of receptor alterations remain largely unknown, but altogether they point towards a central position of laminin-211 in regulating the expression of α7β1 and dystroglycan.
Amelioration of disease in mice
Additional file 1: Supplemental video 1. A 2-year-old laminin α2 chain-deficient mouse ( dy 3K / dy 3K ) overexpressing laminin α1 chain together with a wild-type littermate. The rescue mouse is denoted with a blue pointer at the beginning of the f. Both mice were placed in a new cage. The dy 3K LMα1 mouse is as active as wild-type littermate; it explores the cage and often stands up on its hind limbs. (MPEG 4 MB)
Despite significant therapeutic benefits in mice, it is important to realize that these transgenic approaches are not clinically feasible. Therefore, adenoassociated virus-mediated gene transfer of mini-agrin was tested in dy W /dy W and dy/dy mice. Notably, systemic gene delivery of mini-agrin improved the overall phenotype and muscle function in treated animals .
Several approaches aimed at assuaging the secondary defects in MDC1A, instead of targeting the primary deficiency, have also been undertaken. As increased apoptosis had been suggested to contribute to the pathology of MDC1A, Miller et al. caused either inactivation of the proapoptotic protein Bax or overexpression of the antiapoptotic protein Bcl-2 in dy W /dy W animals [114, 115]; both of these genetic interventions improved the health of the animals. Overexpression of Bcl-2 had no major effect in dystrophin-deficient mice, indicating that Bcl-2-mediated apoptosis is a more significant contributor to the pathogenesis of MDC1A than that of Duchenne muscular dystrophy . The same group also recently explored the use of anti-apoptotic pharmacologic treatment. Interestingly, treatment with minocycline or doxycycline increased the lifespan of dy W /dy W animals and lessened muscle pathology . Similarly, treatment with omigapil, which inhibits GAPDH-Siah1-mediated apoptosis, ameliorated the pathological features in dy W /dy W animals . Recently, it was also established that mitochondria isolated from dy W /dy W muscle are swollen. This is a typical feature of abnormal opening of the permeability transition pore caused by a strong increase in intracellular calcium (which may be detrimental for the muscle cell). Persistent opening may cause mitochondrial rupture and subsequent cell death. Laminin α2 chain-deficient dy W /dy W mice devoid of cyclophilin-D, which is a regulatory protein of the permeability transition pore, displayed reduced muscular dystrophy pathology . Additionally, because enhanced proteasomal degradation is a feature of laminin α2 chain-deficient muscle , we hypothesized that inhibition of the proteasome would lessen the myopathology, and indeed, treatment with the proteasome inhibitor MG-132 significantly improved the lifespan and muscle morphology of dy 3K /dy 3K mice .
Finally, cell therapy has been evaluated in mouse models of MDC1A. Myoblast and CD90-positive cell transplantation led to laminin α2 chain expression in dy/dy and dy 3K /dy 3K mice, respectively, but no further improvement in the animals, was reported [118, 119]. However, bone-marrow transplantation improved life span, growth rate, muscle strength and importantly, respiratory function of dy/dy animals .
Altogether, considering that laminin α2 chain deficiency seems to affect different cellular events, combinatorial treatment strategies (for example, apoptosis and proteasome inhibitors together with replacement therapy) may be relevant for MDC1A. Moreover, bearing in mind that MDC1A is associated with peripheral neuropathy, therapies that also alleviate the neurologic dysfunction should be favored. Previous studies found that motor nerve pathology could not be prevented by muscle-specific expression of laminin α2 chain  and mini-agrin , whereas ubiquitous expression of the laminin α1 chain significantly reduced peripheral neuropathy . In addition, inactivation of Bax s  and treatment with doxycycline  were reported to be beneficial for the condition of motor neuron.
A great deal is known about the structure and function of laminin-211, and advances concerning the development of future therapies have been made for murine laminin α2 chain-deficient muscular dystrophy. Absence of the laminin α2 chain does not only affect skeletal muscle but also several non-muscle tissues. Analysis of these organs has been hampered by the relatively early death of the animals. It would therefore be informative to analyze the non-muscle organs in animals that have been rescued from the muscle defects or to generate mice with a tissue-specific disruption of the laminin α2 chain. Furthermore, the targeted genetic elimination of individual laminin domains (in particular the LG domains) would be valuable to understand their role in vivo. Finally, elucidation of laminin α2 chain-induced signal transduction pathways is an important task. Such studies would be helpful to further clarify the details of laminin α2 chain function to design future treatment for MDC1A.
KIG is a post-doctoral student at the Department of Experimental Medical Science, University of Lund, with a PhD in cell and molecular biology, specializing in preclinical studies of laminins and muscle disease. MD is a professor in muscle biology at the Department of Experimental Medical Science, University of Lund, with a PhD in animal physiology, specializing in preclinical studies of laminins and muscle disease.
cAMP response element binding protein (CREB) binding protein.
This work was supported by Muscular Dystrophy Association. We are very grateful to Professor Volker Straub and the patient and family for their permission to use the photographs.
- Miner JH, Yurchenco PD: Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol 2004, 20: 255-284. 10.1146/annurev.cellbio.20.010403.094555PubMedGoogle Scholar
- Sarass MP Jr, Yan L, Grens A, Zhang X, Agbas A, Huff JK, St John PL, Abrahamson DR: Cloning and biological function of laminin in Hydra vulgaris. Dev Biol 1994, 164: 312-324. 10.1006/dbio.1994.1201Google Scholar
- Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD: A simplified laminin nomenclature. Matrix Biol 2005, 24: 326-332. 10.1016/j.matbio.2005.05.006PubMedGoogle Scholar
- Tzu J, Marinkovich MP: Bridging structure with function: structural, regulatory, and developmental roles of laminins. Int J Biochem Cell Biol 2008, 40: 199-214. 10.1016/j.biocel.2007.07.015PubMed CentralPubMedGoogle Scholar
- McDonald PR, Lustig A, Steinmetz MO, Kammerer RA: Laminin chain assembly is regulated by specific coiled-coil interactions. J Struct Biol 2010, 170: 398-405. 10.1016/j.jsb.2010.02.004Google Scholar
- Timpl R, Rohde H, Robey PG, Rennard SI, Foidart JM, Martin GM: Laminin- a glycoprotein from basement membranes. J Biol Chem 1979, 254: 9933-9937.PubMedGoogle Scholar
- Ehrig K, Leivo I, Argraves WS, Ruoslahti E, Engvall E: Merosin, a tissue-specific basement membrane protein, is a laminin-like protein. Proc Natl Acad Sci USA 1991, 87: 3264-3268. 10.1073/pnas.87.9.3264Google Scholar
- Leivo I, Engvall E: Merosin, a protein specific for basement membranes of Schwann cells, striated muscle, and trophoblast, is expressed late in nerve and muscle development. Proc Natl Acad Sci USA 1988, 85: 1544-1588. 10.1073/pnas.85.5.1544PubMed CentralPubMedGoogle Scholar
- Patton BL, Miner JH, Chiu AY, Sanes JR: Distribution and functions of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol 1997, 139: 1507-1521. 10.1083/jcb.139.6.1507PubMed CentralPubMedGoogle Scholar
- Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, Tomé FMS, Schwartz K, Fardeau M, Tryggvason K, Guicheney P: Mutations in the laminin α2 chain gene (LAMA2) cause merosin-deficient muscular dystrophy. Nat Genet 1995, 11: 216-218. 10.1038/ng1095-216PubMedGoogle Scholar
- Xu H, Christmas P, Wu XR, Wewer UM, Engvall E: Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse. Proc Natl Acad Sci USA 1994, 91: 5572-5576. 10.1073/pnas.91.12.5572PubMed CentralPubMedGoogle Scholar
- Sunada Y, Bernier SM, Utani A, Yamada Y, Campbell KP: Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain to dy locus. J Biol Chem 1994, 269: 13279-13732.Google Scholar
- Paulsson M, Saladin K, Engvall E: Structure of laminin variants: The 300-kDa chains of murine and bovine heart laminin are related to the human placenta merosin heavy chain and replace the a chain in some laminin variants. J Biol Chem 1991, 266: 17545-17551.PubMedGoogle Scholar
- Talts JF, Mann K, Yamada Y, Timpl R: Structural analysis and proteolytic processing of recombinant G domain of mouse laminin α2 chain. FEBS Lett 1998, 426: 71-76. 10.1016/S0014-5793(98)00312-3PubMedGoogle Scholar
- Smirnov SP, McDearmon EL, Li S, Ervasti JM, Tryggvason K, Yurchenco PD: Contributions of the LG modules and furin processing to laminin-2 functions. J Biol Chem 2002, 277: 18928-18937. 10.1074/jbc.M201880200PubMedGoogle Scholar
- Yurchenco PD, O'Rear JJ: Basement membrane assembly. Methods Enzymol 1994, 245: 489-518. full_textPubMedGoogle Scholar
- Colognato H, Yurchenco PD: The laminin α2 expressed by dystrophic dy(2J) mice is defective in its ability to form polymers. Curr Biol 1999, 9: 1327-1330. 10.1016/S0960-9822(00)80056-1PubMedGoogle Scholar
- Talts JF, Andac Z, Gohring W, Brancaccio A, Timpl R: Binding of the G domains of laminin α1 and α2 chains and perlecan to heparin, sulfatides, α-dystroglycan and several extracellular matrix proteins. EMBO J 1999, 18: 863-870. 10.1093/emboj/18.4.863PubMed CentralPubMedGoogle Scholar
- Talts JF, Timpl R: Mutation of a basic sequence in the laminin α2LG3 module leads to a lack of proteolytic processing and has different effects on β1 integrin-mediated cell adhesion and α-dystroglycan binding. FEBS Lett 1999, 458: 319-23. 10.1016/S0014-5793(99)01180-1PubMedGoogle Scholar
- Li S, Liquari P, McKee KK, Harrison D, Patel R, Lee S, Yurchenco PD: Laminin-sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts. J Cell Biol 2005, 169: 179-189. 10.1083/jcb.200501098PubMed CentralPubMedGoogle Scholar
- Sanes JR: The extracellular matrix. In Myology. Volume 1. Edited by: Engel A, Franzini-Armstrong C. New York: McGraw-Hill; 2004:471-488.Google Scholar
- Noakes PG, Gautam M, Mudd J, Sanes JR, Merlie JP: Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin β2. Nature 1995, 374: 258-262. 10.1038/374258a0PubMedGoogle Scholar
- Patton BL, Cunningham JM, Thyboll J, Kortesmaa J, Westerblad H, Edstrom L, Tryggvason K, Sanes JR: Properly formed but improperly localized synaptic specializations in the absence of laminin α4. Nat Neurosci 2001, 4: 597-604. 10.1038/88414PubMedGoogle Scholar
- Nishimune H, Sanes JR, Carlson SS: A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals. Nature 2004, 432: 580-587. 10.1038/nature03112PubMedGoogle Scholar
- Nishimune H, Valdez G, Jarad G, Moulson CL, Müller U, Miner JH, Sanes JR: Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction. J Cell Biol 2008, 182: 1201-1215. 10.1083/jcb.200805095PubMed CentralPubMedGoogle Scholar
- Miner JH, Go G, Cunningham J, Patton BL, Jarad G: Transgenic isolation of skeletal muscle and kidney defects in laminin β2 mutant mice: implications for Pierson syndrome. Development 2006, 133: 967-975. 10.1242/dev.02270PubMed CentralPubMedGoogle Scholar
- Tiger CF, Gullberg D: Absence of laminin α1 chain in the skeletal muscle of dystrophic dy/dy mice. Muscle Nerve 1997, 12: 1515-1524. 10.1002/(SICI)1097-4598(199712)20:12<1515::AID-MUS6>3.0.CO;2-BGoogle Scholar
- Tosney KW, Dehnbostel DB, Erickson CA: Neural crest prefer the myotome's basal lamina over the sclerotome as a substratum. Dev Biol 1994, 163: 389-406. 10.1006/dbio.1994.1157PubMedGoogle Scholar
- Anderson C, Thorsteinsdottir S, Borycki AG: Sonic hedgehog-dependent synthesis of laminin α1 controls basement membrane assembly in the myotome. Development 2009, 136: 3495-3504. 10.1242/dev.036087PubMed CentralPubMedGoogle Scholar
- Sewry CA, Chevallay M, Tomé FM: Expression of laminin subunits in human fetal skeletal muscle. Histochem J 1995, 27: 497-504.PubMedGoogle Scholar
- Pedrosa-Domellöf F, Tiger CF, Virtanen I, Thornell LE, Gullberg D: Laminin chains in developing and adult human myotendinous junctions. J Histochem Cytochem 2000, 48: 201-210.PubMedGoogle Scholar
- Petäjäniemi N, Korhonen M, Kortesmaa J, Tryggvason K, Sekiguchi K, Fujiwara H, Sorokin L, Thornell LE, Wondimu Z, Assefa D, Patarroyo M, Virtanen I: Localization of laminin α4-chain in developing and adult human tissues. J Histochem Cytochem 2002, 50: 1113-1130.PubMedGoogle Scholar
- Tiger CF, Champliaud MF, Pedrosa-Domellöf F, Thornell LF, Ekblom P, Gullberg D: Presence of laminin α5 chain and lack of laminin α1 chain during human muscle development and in muscular dystrophies. J Biol Chem 1997, 272: 28590-28595. 10.1074/jbc.272.45.28590PubMedGoogle Scholar
- Gullberg D, Tiger CF, Velling T: Laminins during muscle development and in muscular dystrophies. Cell Mol Life Sci 1999, 30: 442-460. 10.1007/s000180050444Google Scholar
- Patton BL, Connoll AM, Martin PT, Cunningham JM, Mehta S, Pestronk A, Miner JH, Sanes JR: Distribution of ten laminin chains in dystrophic and regenerating muscles. Neuromuscul Disord 1999, 9: 423-433. 10.1016/S0960-8966(99)00033-4PubMedGoogle Scholar
- Schuler F, Sorokin LM: Expression of laminin isoforms in myogenic cells in vitro and in vivo. J Cell Sci 1995, 108: 3795-3805.PubMedGoogle Scholar
- Vachon PH, Loechel F, Xu H, Wewer UM, Engvall E: Merosin and laminin in myogenesis; specific requirements for merosin in myotubal stability and survival. J Cell Biol 1996, 134: 1483-1497. 10.1083/jcb.134.6.1483PubMedGoogle Scholar
- Miner JH, Cunningham J, Sanes JR: Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin α5 chain. J Cell Biol 1998, 143: 1713-1723. 10.1083/jcb.143.6.1713PubMed CentralPubMedGoogle Scholar
- Edwards MM, Mammadova-Bach E, Alpy F, Klein A, Hicks WL, Roux M, Simon-Assmann P, Smith RS, Orend G, Wu J, Peachey NS, Naggert JK, Lefebvre O, Nishina PM: Mutations in Lama1 disrupt retinal vascular development and inner limiting membrane formation. J Biol Chem 2010, 285: 7697-7711. 10.1074/jbc.M109.069575PubMed CentralPubMedGoogle Scholar
- Hayashi YK, Engvall E, Arikawa-Hirasawa E, Goto K, Koga R, Nonaka I, Sugita H, Arahata K: Abnormal localization of laminin subunits in muscular dystrophies. J Neurol Sci 1993, 119: 53-64. 10.1016/0022-510X(93)90191-ZPubMedGoogle Scholar
- Tomé FM, Evangelista T, Leclerc A, Sunada Y, Manole E, Estournet B, Barois A, Campbell KP, Fardeau M: Congenital muscular dystrophy with merosin deficiency. CR Acad Sci III 1994, 317: 351-357.Google Scholar
- Miyagoe Y, Hanaoka K, Nonaka I, Hayasaka M, Nabeshima Y, Arahata K, Nabeshima Y, Takeda S: Laminin α2 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy. FEBS Lett 1997, 415: 33-39. 10.1016/S0014-5793(97)01007-7PubMedGoogle Scholar
- Kuang W, Xu H, Vachon PH, Engvall E: Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. J Clin Invest 1998, 102: 844-852. 10.1172/JCI3705PubMed CentralPubMedGoogle Scholar
- Cohn RD, Herrmann R, Wewer UM, Voit T: Changes of laminin β2 chain expression in congenital muscular dystrophy. Neuromuscul Disord 1997, 7: 373-378. 10.1016/S0960-8966(97)00072-2PubMedGoogle Scholar
- Sanes JR: The basement membrane/basal lamina of skeletal muscle. J Biol Chem 2003, 278: 12601-12604. 10.1074/jbc.R200027200PubMedGoogle Scholar
- Denzer AJ, Brandenberger R, Gesemann M, Chiquet M, Ruegg MA: Agrin binds to the nerve-muscle basal lamina via laminin. J Cell Biol 1997, 137: 671-683. 10.1083/jcb.137.3.671PubMed CentralPubMedGoogle Scholar
- Feltri ML, Wrabetz L: Laminins and their receptors in Schwann cells and hereditary neuropathies. J Peripher Nerv Syst 2005, 10: 128-143. 10.1111/j.1085-9489.2005.0010204.xPubMedGoogle Scholar
- Gawlik KI, Li JY, Petersen Å, Durbeej M: Laminin α1 chain improves laminin α2 chain deficient neuropathy. Hum Mol Genet 2006, 15: 2690-2700. 10.1093/hmg/ddl201PubMedGoogle Scholar
- Engvall E, Earwicker D, Haaparanta T, Ruoslahti E, Sanes JR: Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regul 1990, 10: 731-40.Google Scholar
- Kuang W, Xu H, Vachon PH, Engvall E: Disruption of the lama2 gene in embryonic stem cells: laminin α2 is necessary for the sustenance of mature muscle cells. Exp Cell Res 1998, 241: 117-125. 10.1006/excr.1998.4025PubMedGoogle Scholar
- Desaki J, Matsuda S, Sakanaka M: Morphological changes of neuromuscular junctions in the dystrophic (dy) mouse: a scanning and transmission electron microscopic study. J Electron Microsc (Tokyo) 1995, 44: 59-65.Google Scholar
- Gubler MC: Inherited diseases of the glomerular basement membrane. Nat Clin Pract Nephrol 2008, 4: 24-37. 10.1038/ncpneph0671PubMedGoogle Scholar
- Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, Yang B, Koepnick K, Francke U, Campbell KP: Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization. Hum Mol Genet 1993, 2: 1651-1657. 10.1093/hmg/2.10.1651PubMedGoogle Scholar
- Campbell KP, Kahl SD: Association of dystrophin and an integral membrane glycoprotein. Nature 1989, 338: 259-262. 10.1038/338259a0PubMedGoogle Scholar
- Ervasti JM, Campbell KP: A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 1993, 122: 809-823. 10.1083/jcb.122.4.809PubMedGoogle Scholar
- Yoshida-Moriguchi T, Yu L, Stalnaker SH, Davis S, Kunz S, Madson M, Oldstone MB, Schachter H, Wells L, Campbell KP: O-mannosyl phosphorylation of α-dystroglycan is required for laminin binding. Science 2010, 327: 88-92. 10.1126/science.1180512PubMed CentralPubMedGoogle Scholar
- Tisi D, Talts JF, Timpl R, Hohenester E: Structure of the C-terminal laminin G-like domain pair of the laminin α2 chain harbouring binding sites for α-dystroglycan and heparin. EMBO J 2000, 19: 1432-1440. 10.1093/emboj/19.7.1432PubMed CentralPubMedGoogle Scholar
- von der Mark H, Durr J, Sonnenberg A, von der Mark K, Deutzmann R, Goodman SL: Skeletal myoblasts utilize a novel β1-series integrin and not α6β1 for binding to the E8 and T8 fragments of laminin. J Biol Chem 1991, 266: 23593-23601.PubMedGoogle Scholar
- Song WK, Wang W, Foster RF, Bielser DA, Kaufman SJ: H36-α7 is a novel integrin α chain that is developmentally regulated during skeletal myogenesis. J Cell Biol 1992, 117: 643-657. 10.1083/jcb.117.3.643PubMedGoogle Scholar
- Vachon PH, Xu H, Liu L, Loechel F, Hayashi Y, Arahata K, Reed JC, Wewer UM, Engvall E: Integrins (α7β1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy. J Clin Invest 1997, 10: 1870-1881. 10.1172/JCI119716Google Scholar
- Mayer U: Integrins: redundant or important players in skeletal muscle? J Biol Chem 2003, 278: 14587-14590. 10.1074/jbc.R200022200PubMedGoogle Scholar
- Conti FJ, Monkley SJ, Wood MR, Critchley DR, Muller U: Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junction. Development 2009, 136: 3597-3606. 10.1242/dev.035857PubMed CentralPubMedGoogle Scholar
- Wang HV, Chang LW, Brixius K, Wickström SA, Montanez E, Thievessen I, Schwander M, Muller U, Bloch W, Mayer U, Fässler R: Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage. J Cell Biol 2008, 180: 1037-1049. 10.1083/jcb.200707175PubMed CentralPubMedGoogle Scholar
- Häger M, Bigotti MG, Meszaros R, Carmignac V, Holmberg J, Allamand V, Åkerlund M, Kalamajski S, Brancaccio A, Mayer U, Durbeej M: Cib2 binds integrin α7Bβ1D and is reduced in laminin α2 chain-deficient muscular dystrophy. J Biol Chem 2008, 283: 24760-247695.PubMed CentralPubMedGoogle Scholar
- Lisi MT, Cohn RD: Congenital muscular dystrophies: new aspects of an expanding group of disorders. Biochim Biophys Acta 2007, 1772: 159-172.PubMedGoogle Scholar
- Hayashi YK, Chou FL, Engvall E, Ogawa M, Matsuda C, Hirabayashi S, Yokochi K, Ziober BL, Kramer RH, Kaufman SJ, Ozawa E, Goto Y, Nonaka I, Tsukahara T, Wang JZ, Hoffman EP, Arahata K: Mutations in the integrin α7 gene cause congenital myopathy. Nat Genet 1998, 19: 94-97. 10.1038/ng0598-94PubMedGoogle Scholar
- Guo C, Willem M, Werner A, Raivich G, Emerson M, Neyses L, Mayer U: Absence of α7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy. Hum Mol Genet 2006, 15: 989-98. 10.1093/hmg/ddl018PubMedGoogle Scholar
- Rooney JE, Welser JV, Dechert MA, Flintoff-Dye NL, Kaufman SJ, Burkin DJ: Severe muscular dystrophy in mice that lack dystrophin and α7 integrin. J Cell Sci 2006, 119: 2185-2195. 10.1242/jcs.02952PubMedGoogle Scholar
- Han R, Kanagawa M, Yoshida-Moriguchi T, Rader EP, Ng RA, Michele DE, Muirhead DE, Kunz S, Moore SA, Iannaccone ST, Miyake K, McNeil PL, Mayer U, Oldstone MBA, Faulkner JA, Campbell KP: Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of α-dystroglycan. Proc Natl Acad Sci USA 2009, 106: 12573-12579. 10.1073/pnas.0906545106PubMed CentralPubMedGoogle Scholar
- Gawlik KI, Åkerlund M, Carmignac V, Elamaa H, Durbeej M: Distinct roles for laminin globular domains in laminin α1 chain mediated rescue of murine laminin α2 chain deficiency. PLoS ONE 2010, 5: e11549. 10.1371/journal.pone.0011549PubMed CentralPubMedGoogle Scholar
- Yang B, Jung D, Motto D, Meyer J, Koretzky G, Campbell KP: SH3 domain-mediated interaction of dystroglycan and Grb2. J Biol Chem 1995, 270: 11711-11714. 10.1074/jbc.270.20.11711PubMedGoogle Scholar
- Zhou YW, Oak SA, Senogles SE, Jarrett HW: Laminin-α1 globular domains 3 and 4 induce heterotrimeric G protein binding to α-syntrophin's PDZ domain and alter intracellular Ca 2+ in muscle. Am J Physiol Cell Physiol 2005, 288: C377-388. 10.1152/ajpcell.00279.2004PubMedGoogle Scholar
- Zhou Y, Jiang D, Thomason DB, Jarrett HW: Laminin-induced activation of Rac1 and JNKp46 is initiated by Src family kinases and mimics the effects of skeletal muscle contraction. Biochemistry 2007, 46: 14907-14916. 10.1021/bi701384kPubMed CentralPubMedGoogle Scholar
- Langenbach KJ, Rando TA: Inhibition of dystroglycan binding to laminin disrupts the PI3K/AKT pathway and survival signaling in muscle cells. Muscle Nerve 2002, 26: 644-653. 10.1002/mus.10258PubMedGoogle Scholar
- Xiong Y, Zhou Y, Jarrett HW: Dystrophin glycoprotein complex-associated Gβγ subunits activate phosphatidylinositol-3-kinase/Akt signaling in skeletal muscle in a laminin-dependent manner. J Cell Physiol 2009, 219: 402-414. 10.1002/jcp.21684PubMed CentralPubMedGoogle Scholar
- Laprise P, Poirier EM, Vezina A, Rivard N, Vachon PH: Merosin-integrin promotion of skeletal myofiber cell survival: Differentiation state-distinct involvement of p60Fyn tyrosine kinase and p38alpha stress-activated MAP kinase. J Cell Physiol 2002, 191: 69-81. 10.1002/jcp.10075PubMedGoogle Scholar
- Suzuki N, Yokoyama F, Nomizu M: Functional sites in the laminin alpha chains. Conn Tiss Res 2005, 46: 142-152. 10.1080/03008200591008527Google Scholar
- Allamand V, Guicheney P: Merosin-deficient muscular dystrophy, autosomal recessive (MDC1A, MIM#156225, LAMA2 gene coding for α2 chain of laminin). Eur J Hum Genet 2002, 10: 91-94. 10.1038/sj.ejhg.5200743PubMedGoogle Scholar
- Voit T, Tomé FS: The congenital muscular dystrophies. In Myology. Volume 2. Edited by: Angel A, Franzini-Armstrong C. New York: McGraw-Hill; 2004:1203-1238.Google Scholar
- Geranmayeh F, Clement E, Feng LH, Sewry C, Pagan J, Mein R, Abbs S, Brueton L, Childs AM, Jungbluth H, De Goede CG, Lynch B, Lin JP, Chow G, Sousa C, O'Mahony O, Majumdar A, Straub V, Bushby K, Muntoni F: Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. Neuromuscul Disord 2010, 4: 241-250. 10.1016/j.nmd.2010.02.001Google Scholar
- Mostacciuolo ML, Miorin M, Martinello F, Angelini C, Perini P, Trevisan CP: Genetic epidemiology of congenital muscular dystrophy in a sample from north-east Italy. Hum Genet 1996, 97: 277-279. 10.1007/BF02185752PubMedGoogle Scholar
- Wang CH, Bonnemann CG, Rutkowski A, Sejersen T, Bellini J, Battista V, Florence JM, Schara U, Schuler PM, Wahbi K, Aloysius A, Bash RO, Béroud C, Bertini E, Bushby K, Cohn RD, Connolly AM, Deconinck N, Desguerre I, Eagle M, Estournet-Mathiaud B, Ferreiro A, Fujak A, Goemans N, Iannaccone ST, Jouinot P, Main M, Melacini P, Mueller-Felber W, Muntoni F, Nelson LL, Rahbek J, Quijano-Roy S, Sewry C, Storhaug K, Simonds A, Tseng B, Vajsar J, Vianello A, Zeller R: Consensus statement on standard care for congenital muscular dystrophies. J Child Neurol 2010, 25: 1559-1581. 10.1177/0883073810381924PubMedGoogle Scholar
- Guo LT, Zhang XU, Kuang W, Xu H, Liu LA, Vilquin JT, Miyagoe-Suzuki Y, Takeda S, Ruegg MA, Wewer UM, Engvall E: Laminin α2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice. Neuromusc Disord 2003, 3: 207-215. 10.1016/s0960-8966(02)00266-3Google Scholar
- Chun SJ, Rasband MN, Sidman RL, Habib AA, Vartanian T: Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. J Cell Biol 2003, 163: 397-408. 10.1083/jcb.200304154PubMed CentralPubMedGoogle Scholar
- Xu H, Wu XR, Wewer UM, Engvall E: Murine muscular dystrophy caused by a mutation in the laminin α2 (Lama2) gene. Nat Genet 1994, 8: 297-302. 10.1038/ng1194-297PubMedGoogle Scholar
- Sunada Y, Bernier SM, Utani A, Yamada Y, Campbell KP: Identification of a novel mutant transcript of laminin α2 chain gene responsible for muscular dystrophy and dysmyelination in dy2J mice. Hum Mol Genet 1995, 4: 1055-1061. 10.1093/hmg/4.6.1055PubMedGoogle Scholar
- Patton BL, Wang B, Tarumi YS, Seburn KL, Burgess RW: A single point mutation in the LN domain of LAMA2 causes muscular dystrophy and peripheral amyelination. J Cell Sci 2008, 121: 1593-1604. 10.1242/jcs.015354PubMedGoogle Scholar
- Kuang W, Xu H, Vilquin JT, Engvall E: Activation of the lama2 gene in muscle regeneration: abortive regeneration in laminin α2-deficiency. Lab Invest 1999, 79: 1601-1613.PubMedGoogle Scholar
- Hayashi YK, Tezak Z, Momoi T, Nonaka I, Garcia CA, Hoffman EP, Arahata K: Massive muscle cell degeneration in the early stage of merosin-deficient congenital muscular dystrophy. Neuromuscul Disord 2001, 11: 350-359. 10.1016/S0960-8966(00)00203-0PubMedGoogle Scholar
- Ervasti JM, Campbell KP: Membrane organization of the dystrophin-glycoprotein complex. Cell 1993, 66: 1121-1131. 10.1016/0092-8674(91)90035-WGoogle Scholar
- Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL: Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA 1993, 90: 3710-3714. 10.1073/pnas.90.8.3710PubMed CentralPubMedGoogle Scholar
- Hall TE, Bryson-Richardson RJ, Berger S, Jacoby AS, Cole NJ, Hollway GE, Berger J, Currie PD: The zebrafish candyfloss mutant implies extracellular matrix adhesion failure in laminin α2-deficient congenital muscular dystrophy. Proc Natl Acad Sci USA 2007, 104: 7093-7097.Google Scholar
- Erb M, Meinen S, Barzaghi P, Sumanovski LT, Courdier-Fruh I, Ruegg MA, Meier T: Omigapil ameliorates the pathology of muscle dystrophy caused by laminin-α2 deficiency. J Pharmacol Exp Ther 2009, 331: 787-795. 10.1124/jpet.109.160754PubMedGoogle Scholar
- Sandri M: Autophagy in skeletal muscle. FEBS Lett 2010, 584: 1411-1416. 10.1016/j.febslet.2010.01.056PubMedGoogle Scholar
- Carmignac V, Quéré R, Durbeej M: Proteasome inhibition improves the muscle of laminin α2 chain-deficient mice. Hum Mol Genet 2011, 20: 541-552. 10.1093/hmg/ddq499PubMedGoogle Scholar
- Bonuccelli G, Sotiga F, Schubert W, Park DS, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, Lisanti MP: Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and localization of dystrophin and dystrophin-associated proteins. Am J Path 2003, 163: 1663-1675. 10.1016/S0002-9440(10)63523-7PubMed CentralPubMedGoogle Scholar
- Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, Blaauw B, Urciuolo A, Tiepolo T, Merlini L, Maraldi NM, Bernardi P, Sandri M, Bonaldo P: Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat Med 2010, 16: 1313-1321. 10.1038/nm.2247PubMedGoogle Scholar
- Ringelmann B, Roder C, Hallmann R, Maley M, Davies M, Grounds M, Sorokin L: Expression of laminin α1, α2, α4, and α5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice. Exp Cell Res 1999, 246: 165-182. 10.1006/excr.1998.4244PubMedGoogle Scholar
- Talts JF, Sasaki T, Miosge N, Gohring W, Mann K, Mayne R, Timpl R: Structural and functional analyses of the recombinant G domain of the laminin α4 chain and its proteolytic processing in tissues. J Biol Chem 2000, 275: 35192-35199. 10.1074/jbc.M003261200PubMedGoogle Scholar
- Porter JD, Karathanasis P: Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is maintained but is not mechanistic in muscle sparing. Cell Tissue Res 1998, 292: 495-501. 10.1007/s004410051078PubMedGoogle Scholar
- Nyström A, Holmblad J, Pedrosa-Domellöf F, Sasaki T, Durbeej M: Extraocular muscle is spared upon complete laminin α2 chain deficiency: comparative expression of laminin and integrin isoforms. Matrix Biol 2006, 25: 382-385.PubMedGoogle Scholar
- Hodges BS, Hayashi YK, Nonaka I, Wang A, Arahata K, Kaufman SJ: Altered expression of the α7β1 integrin in human and murine muscular dystrophies. J Cell Sci 1997, 110: 2873-2881.PubMedGoogle Scholar
- Cohn RD, Mayer U, Saher G, Herrmann R, van der Flier A, Sonnenberg A, Sorokin L, Voit T: Secondary reduction of integrin α7B in laminin α2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle. J Neurol Sci 1999, 63: 140-152. 10.1016/S0022-510X(99)00012-XGoogle Scholar
- Gawlik KI, Mayer U, Blomberg K, Sonnenberg A, Ekblom P, Durbeej M: Laminin α1 chain mediated reduction of laminin α2 chain deficient muscular dystrophy involves integrin α7β1 and dystroglycan. FEBS Lett 2006, 580: 1759-1765. 10.1016/j.febslet.2006.02.027PubMedGoogle Scholar
- Moll J, Barzaghi P, Lin S, Bezakova G, Lochmuller H, Engvall E, Muller U, Ruegg MA: An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy. Nature 2001, 413: 302-307. 10.1038/35095054PubMedGoogle Scholar
- Jimenez-Mallebrera C, Torelli S, Feng L, Kim J, Godfrey C, Clement E, Mein R, Abbs S, Brown SC, Campbell KP, Kröger S, Talim B, Topaloglu H, Quinlivan R, Roper H, Childs AM, Kinali M, Sewry CA, Muntoni F: A comparative study of α-dystroglycan glycosylation in dystroglycanopathies suggests that the hypoglycosylation of alpha-dystroglycan does not consistently correlate with clinical severity. Brain Pathol 2009, 19: 596-611. 10.1111/j.1750-3639.2008.00198.xPubMed CentralPubMedGoogle Scholar
- Bentzinger CF, Barzaghi P, Lin S, Ruegg MA: Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-α2-deficient mice. FASEB J 2005, 19: 934-942. 10.1096/fj.04-3376comPubMedGoogle Scholar
- Gawlik K, Miyagoe-Suzuki Y, Ekblom P, Takeda S, Durbeej M: Laminin α1 chain reduces muscular dystrophy in laminin α2 chain deficient mice. Hum Mol Genet 2004, 13: 1775-1784. 10.1093/hmg/ddh190PubMedGoogle Scholar
- Xu R, Chandrasekharan K, Yoon JH, Camboni M, Martin PT: Overexpression of the cytotoxic T cell (CT) carbohydrate inhibits muscular dystrophy in the dy W mouse model of congenital muscular dystrophy 1A. Am J Path 2007, 171: 181-199. 10.2353/ajpath.2007.060927PubMed CentralPubMedGoogle Scholar
- Meinen S, Barzaghi P, Lin S, Lochmuller H, Ruegg MA: Linker molecules between laminins and dystroglycan ameliorate laminin- α2-deficient muscular dystrophy at all disease stages. J Cell Biol 2007, 176: 979-993. 10.1083/jcb.200611152PubMed CentralPubMedGoogle Scholar
- Gawlik KI, Durbeej M: Transgenic overexpression of laminin α1 chain in laminin α2 chain-deficient mice rescues the disease throughout the lifespan. Muscle Nerve 2010, 42: 30-37. 10.1002/mus.21616PubMedGoogle Scholar
- von der Mark H, Williams I, Wendler O, Sorokin L, von der Mark K, Pöschl E: Alternative splice variants of α7β1 integrin selectively recognize different laminin isoforms. J Biol Chem 2002, 277: 6012-6016. 10.1074/jbc.M102188200PubMedGoogle Scholar
- Qiao C, Li J, Zhu T, Draviam R, Watkins S, Ye X, Chen C, Li J, Xiao X: Amelioration of laminin-α2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin. Proc Natl Acad Sci USA 2005, 102: 11999-12004. 10.1073/pnas.0502137102PubMed CentralPubMedGoogle Scholar
- Girgenrath M, Dominov JA, Kostek CA, Miller JB: Inhibition of apoptosis improves outcome in a model of congenital muscular dystrophy. J Clin Invest 2004, 114: 1635-1639.PubMed CentralPubMedGoogle Scholar
- Dominov JA, Kravetz AJ, Ardelt M, Kostek CA, Beermann ML, Miller JB: Muscle-specific BCL2 expression ameliorates muscle disease in laminin α2-deficient, but not in dystrophin-deficient, mice. Hum Mol Genet 2005, 14: 1029-1040. 10.1093/hmg/ddi095PubMedGoogle Scholar
- Girgenrath M, Beermann ML, Vishnudas VK, Homma S, Miller JB: Pathology is alleviated by doxycycline in a laminin-α2-null model of congenital muscular dystrophy. Ann Neurol 2009, 65: 47-56. 10.1002/ana.21523PubMed CentralPubMedGoogle Scholar
- Millay DP, Sargent MA, Osinska H, Baines CP, Barton ER, Vaugniaux G, Sweeney HL, Robbins J, Molkentin JD: Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat Med 2008, 14: 442-447. 10.1038/nm1736PubMed CentralPubMedGoogle Scholar
- Vilquin JT, Guerette B, Puymirat J, Yaffe D, Tome FMS, Fardeau M, Fiszman M, Schwartz K, Tremblay JP: Myoblast transplantations lead to the expression of the laminin α2 chain in normal and dystrophic (dy/dy) mouse muscles. Gene Therapy 1999, 6: 792-800. 10.1038/sj.gt.3300889PubMedGoogle Scholar
- Fukada S, Yamamoto Y, Segawa M, Sakamoto K, Nakajima M, Sato M, Morokawa D, Uezumi A, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H: CD90-postive cells, an additional cell population, produce laminin α2 chain upon transplantation in dy 3k / dy 3k mice. Exp Cell Res 2007, 314: 193-203. 10.1016/j.yexcr.2007.09.020PubMedGoogle Scholar
- Hagiwara H, Ohsawa Y, Asakura S, Murakami T, Teshima T, Sunada Y: Bone marrow transplantation improves outcome in a mouse model of congenital muscular dystrophy. FEBS Lett 2006, 580: 4463-4468. 10.1016/j.febslet.2006.07.015PubMedGoogle Scholar
- Pillers DA, Kempton JB, Duncan NM, Pang J, Dwinnel SJ, Trune DR: Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy. Mol Genet Metab 2002, 76: 217-224. 10.1016/S1096-7192(02)00039-2PubMedGoogle Scholar
- Wagner WJ, Chang AC, Owens J, Hong MJ, Brooks A, Coligan JE: Aberrant development of thymocytes in mice lacking laminin-2. Dev Immunol 2000, 7: 179-193. 10.1155/2000/90943Google Scholar
- Nakagawa M, Miyagoe-Suzuki Y, Ikezoe K, Miyata Y, Nonaka I, Harii K, Takeda S: Schwann cell myelination occurred without basal lamina formation in laminin α2 chain-null mutant (dy 3K /dy 3K ) mice. Glia 2001, 35: 101-110. 10.1002/glia.1075PubMedGoogle Scholar
- Häger M, Gawlik K, Nyström A, Sasaki T, Durbeej M: Laminin α1 chain corrects male infertility caused by absence of laminin α2 chain. Am J Path 2005, 167: 823-833.PubMed CentralPubMedGoogle Scholar
- Yuasa K, Fukumoto S, Kamasaki Y, Yamada A, Fukumoto E, Kanaoka K, Saito K, Harada H, Arikawa-Hirasawa E, Miyagoe-Suzuki Y, Takeda S, Okamoto K, Kato Y, Fujiwara T: Laminin α2 is essential for odontoblast differentiation regulating dentin sialoprotein expression. J Biol Chem 2004, 279: 10286-10292. 10.1074/jbc.M310013200PubMedGoogle Scholar
- Besse S, Allamand V, Vilquin JT, Li Z, Poirier C, Vignier N, Hori H, Guenet JL, Guicheney P: Spontaneous muscular dystrophy caused by a retrotransposal insertion in the mouse laminin α2 chain gene. Neuromuscul Disord 2003, 13: 216-222. 10.1016/s0960-8966(02)00278-xPubMedGoogle Scholar
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