Key result
Both hypertrophic and dilated cardiomyopathic hamsters share a common genomic deletion in the delta-sarcoglycan gene, resulting in a deficiency of delta-SG transcripts and loss of protein.
The study identifies a deletion in the delta-sarcoglycan gene as the common cause of both hypertrophic and dilated cardiomyopathies in the CM hamster model, highlighting its role in stabilizing the sarcolemma.
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Delta-SG defect links HCM and DCM in hamsters; leaves open translation to human disease mechanisms.
Cardiomyopathy (CM) is a primary degenerative disease of myocardium and is traditionally categorized into hypertrophic and dilated CMs (HCM and DCM) according to its gross appearance. Cardiomyopathic hamster (CM hamster), a representative model of human hereditary CM, has HCM and DCM inbred sublines, both of which descend from the same ancestor. Herein we show that both HCM and DCM hamsters share a common defect in a gene for delta-sarcoglycan (delta-SG), the functional role of which is yet to be characterized. A breakpoint causing genomic deletion was found to be located at 6.1 kb 5' upstream of the second exon of delta-SG gene, and its 5' upstream region of more than 27.4 kb, including the authentic first exon of delta-SG gene, was deleted. This deletion included the major transcription initiation site, resulting in a deficiency of delta-SG transcripts with the consequent loss of delta-SG protein in all the CM hamsters, despite the fact that the protein coding region of delta-SG starting from the second exon was conserved in all the CM hamsters. We elucidated the molecular interaction of dystrophin-associated glycoproteins including delta-SG, by using an in vitro pull-down study and ligand overlay assay, which indicates the functional role of delta-SG in stabilizing sarcolemma. The present study not only identifies CM hamster as a valuable animal model for studying the function of delta-SG in vivo but also provides a genetic target for diagnosis and treatment of human CM.
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Sakamoto et al. (1997) studied Cardiomyopathy (HCM and DCM). delta-sarcoglycan (delta-SG) gene mutation was evaluated on Genomic deletion and loss of delta-SG protein. Both hypertrophic and dilated cardiomyopathic hamsters share a common genomic deletion in the delta-sarcoglycan gene, resulting in a deficiency of delta-SG transcripts and loss of protein.
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