Spontaneous muscular dystrophy caused by a retrotransposal insertion in the mouse laminin α2 chain gene

Abstract

We identified a novel spontaneous mouse model of human congenital muscular dystrophy with laminin α2 chain deficiency, named dy Pas /dy Pas . Homozygous animals rapidly developed a progressive muscular dystrophy leading to premature death. Immunohistological and biochemical analyses demonstrated the absence of laminin α2 chain expression in skeletal muscle. Analysis of the laminin α2 chain cDNA showed the insertion of the long terminal repeat of an intracisternal A-particle gene. In addition, a 6.1 kb insertion composed of retrotransposon elements was identified in the Lama2 sequence. The dy Pas /dy Pas mouse is thus the first spontaneous mutant with a complete laminin α2 chain deficiency in which the mutation has been identified.