The Muscular Dystrophy with Myositis (mdm) Mouse Mutation Disrupts a Skeletal Muscle-Specific Domain of Titin.
Genomics 2002 Feb; 79(2):146-9.
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.
Garvey, S M.; Rajan, C; Lerner, A P.; Frankel, W N.; and Cox, G A., "The Muscular Dystrophy with Myositis (mdm) Mouse Mutation Disrupts a Skeletal Muscle-Specific Domain of Titin." (2002). Faculty Research 2000 - 2009. 353.