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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

Hamster

   

   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

Mouse

   

   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

Drosophila

   

   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

Mild

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)

Zebrafish

   

   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.