The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin
The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin
复制标题
DOI：
10.1006/geno.2002.6685
复制
发表时间：
2002-02-01
期刊：
影响因子：
4.4
通讯作者：
Cox, GA
中科院分区：
文献类型：
--
作者：
Garvey, SM;Rajan, C;Cox, GA
肌萎缩症伴肌炎（mdm）是一种隐性小鼠突变，可导致严重和进行性肌肉变性。在这里，我们报告了mdm突变的鉴定，作为一个复杂的重排，包括titin （Ttn）基因的缺失和LINE插入。突变的等位基因特异性剪接导致TTN的N2A区域缺失83个氨基酸，该区域被认为与人类肢带肌营养不良2A型（LGMD2A）基因的产物calpain-3 （CAPN3）结合。Ttn（mdm）突变小鼠可以作为人类胫骨肌营养不良的模型，其定位于2q31的Ttn位点，并显示类似于mdm骨骼肌中观察到的CAPN3的二次减少。这是首次证明Ttn突变与肌营养不良有关，并提供了一种新的动物模型来测试Ttn和CAPN3之间的功能相互作用。
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.