A common disease-associated missense mutation in alpha-sarcoglycan fails to cause muscular dystrophy in mice.

ABSTRACT: Limb-girdle muscular dystrophy type 2D (LGMD2D) is caused by autosomal recessive mutations in the alpha-sarcoglycan gene. An R77C substitution is the most prevalent cause of the disease, leading to disruption of the sarcoglycan-sarcospan complex. To model this common mutation, we generated knock-in mice with an H77C substitution in alpha-sarcoglycan. The floxed neomycin (Neo)-cassette retained at the targeted H77C alpha-sarcoglycan locus caused a loss of alpha-sarcoglycan expression, resulting in muscular dystrophy in homozygotes, whereas Cre-mediated deletion of the floxed Neo-cassette led to recovered H77C alpha-sarcoglycan expression. Contrary to expectations, mice homozygous for the H77C-encoding allele expressed both this mutant alpha-sarcoglycan and the other components of the sarcog

SUBMITTER: Kobuke K 

PROVIDER: S-EPMC2713597 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature