Table 1.
Animal models of δ-sarcoglycan deficiencya
| 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 |
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.