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Table 1 Animal models of δ-sarcoglycan deficiencya

From: δ-Sarcoglycan-deficient muscular dystrophy: from discovery to therapeutic approaches

Species Genesis Effect on protein/DGC components Phenotype
   BIO 14.6 Naturally occurring, autosomal recessive mutation (30-kb deletion in exons 1 and 2) [44] Loss of δ- and β-SG
Reduction of α- and γ-SG [47, 54]
Reduction in α-dystroglycan [47]
Normal dystrophin
Compensatory hypertrophic CM leading to dilated CM
Sarcolemmal damage (increased EBD uptake)
   TO-2 Cross-breeding (30-kb deletion in exons 1 and 2) Complete loss of SG complex
Translocation of dystrophin to cytoplasm [150]
Severe dilated CM
LV dysfunction from 8 weeks [151]
Gait disturbances [152]
   J2N-k Cross-breeding (BIO 14.6 × golden hamster, then consecutive sib mating) [153] Uncharacterized? Cardiac contractile dysfunction
Dilated CM from 20 weeks [90]
Elevated CK level
   UMX7.1 or CHF147 Cross-breeding (BIO 14.6 × normal controls) [154] Uncharacterized? Dilated CM
Progressive LV dysfunction [155]
Reduced life expectancy (190 days)
Early skeletal muscle pathology (10 to 15 days)
Focal necrosis
Unselective muscle involvement
   Sgcd-/- (C57BL6 background) Transgenic (vector-mediated, knockdown-targeted replacement of exon 2, which encodes the entire TM domain and part of the intracellular domain) [57] Loss of whole SG complex and sarcospan Limb-girdle pattern of muscle involvement
Focal areas of necrosis
Cardiomyopathy from 8 weeks, ECG abnormalities
Increased probability of spontaneous death at 6 months
   Sgcd-/- (129SvJ/129SvEms- +Ter/J background) Transgenic (vector-mediated replacement of exon 2; homozygotes generated from heterozygote matings) [56], resultant δ-SG mRNA lacking 201-bp region. Loss of all SGs (including ε-SG) in muscle microsomes on immunoblot despite normal levels of transcription Premature death: only 50% survival at 28 weeks
Elevated CK
Regional degeneration/regeneration, calcification, inflammatory infiltration, perivascular fibrosis and increased EBD uptake on muscle histology
Cardiac histological changes at 12 weeks
Reduced force generation in response to eccentric contractions
   Line 840 Engineered (large deletion by P element excision) [65] Loss of whole δ-SG protein
Effect on other DGC components uncharacterized
Shortened lifespan
Progressive impairment in locomotive ability
Reduced heart tube function
Abnormal flight muscles
No regeneration
   Line 28 Engineered (small deletion by P element excision) [65] Loss of cytoplasmic region of δ-SG only
Effect on other DGC components uncharacterized
Near-normal lifespan
Normal cardiac function
Normal locomotive function
Caenorhabditis elegans    
   F07H5.2 RNA interference (animals fed or injected with dsRNA corresponding to 500- to 700-bp exon-rich region) [64] Uncharacterized? Phenotype similar to dystrophin KO (dys-1) (bending of head with forward movement, hyperactivity, hypercontraction)
   N/A Morpholino knockdown of δ-SG [67] Downregulation of δ-, β- and γ-SGs Disorganized muscle development
Reduced movement 5 dpf
   N/A Morpholino knockdown of δ-SG [66] Uncharacterized? Severe abnormality of skeletal and cardiac muscle
Delayed cardiac development and abnormal cardiac differentiation
Dead by 5 dpf
  1. aCM, cardiomyopathy; dpf, days postfertilization; KO, knockout; SG, sarcoglycan; EBD, Evans blue dye; LV, left ventricular; CK, creatine kinase; DGC, dystrophin-glycoprotein complex; ECG, electrocardiogram; Sgcd-/-, δ-sarcoglycan-deficient; dsRNA, double-stranded RNA.