Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies
Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies
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DOI：
10.1093/hmg/ddq388
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发表时间：
2010-12-01
影响因子：
3.5
通讯作者：
Richard, Isabelle
中科院分区：
文献类型：
--
作者：
Charton, Karine;Daniele, Nathalie;Richard, Isabelle
The dominant tibial muscular dystrophy (TMD) and recessive limb-girdle muscular dystrophy 2J are allelic disorders caused by mutations in the C-terminus of titin, a giant sarcomeric protein. Both clinical presentations were initially identified in a large Finnish family and linked to a founder mutation (FINmaj). To further understand the physiopathology of these two diseases, we generated a mouse model carrying the FINmaj mutation. In heterozygous mice, dystrophic myopathology appears late at 9 months of age in few distal muscles. In homozygous (HO) mice, the first signs appear in the Soleus at 1 month of age and extend to most muscles at 6 months of age. Interestingly, the heart is also severely affected in HO mice. The mutation leads to the loss of the very C-terminal end of titin and to a secondary deficiency of calpain 3, a partner of titin. By crossing the FINmaj model with a calpain 3-deficient model, the TMD phenotype was corrected, demonstrating a participation of calpain 3 in the pathogenesis of this disease.
