The Muscular Dystrophy with Myositis (mdm) Mouse Mutation Disrupts a Skeletal Muscle-Specific Domain of Titin.
Document Type
Article
Publication Date
2002
First Page
146
Last Page
149
JAX Source
Genomics 2002 Feb; 79(2):146-9.
Abstract
Muscular dystrophy with myositis (mdm) is a recessive mouse mutation that causes severe and progressive muscular degeneration. Here we report the identification of the mdm mutation as a complex rearrangement that includes a deletion and a LINE insertion in the titin (Ttn) gene. Mutant allele-specific splicing results in the deletion of 83 amino acids from the N2A region of TTN, a domain thought to bind calpain-3 (CAPN3) the product of the human limb-girdle muscular dystrophy type 2A (LGMD2A) gene. The Ttn(mdm) mutant mouse may serve as a model for human tibial muscular dystrophy, which maps to the TTN locus at 2q31 and shows a secondary reduction of CAPN3 similar to that observed in mdm skeletal muscle. This is the first demonstration that a mutation in Ttn is associated with muscular dystrophy and provides a novel animal model to test for functional interactions between TTN and CAPN3.
Recommended Citation
Garvey SM,
Rajan C,
Lerner AP,
Frankel WN,
Cox GA.
The Muscular Dystrophy with Myositis (mdm) Mouse Mutation Disrupts a Skeletal Muscle-Specific Domain of Titin. Genomics 2002 Feb; 79(2):146-9.