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Genomics. 2002 Feb;79(2):146-9.

The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin.

Author information

1
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.

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.

PMID:
11829483
DOI:
10.1006/geno.2002.6685
[Indexed for MEDLINE]

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