Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies

Karine Charton; Nathalie Danièle; Anna Vihola; Carinne Roudaut; Evelyne Gicquel; François Monjaret; Anne Tarrade; Jaakko Sarparanta; Bjarne Udd; Isabelle Richard

Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies

Karine Charton ^{1, 2} Nathalie Danièle ^{1, 2} Anna Vihola ³ Carinne Roudaut ^{1, 2} Evelyne Gicquel ^{1, 2} François Monjaret ^{1, 2} Anne Tarrade ⁴ Jaakko Sarparanta ³ Bjarne Udd ^{3, 5} Isabelle Richard ^{1, 2}

1 GENETHON

2 LAMBE - UMR 8587 - Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement

3 Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki

4 SABNP - Structure et activité des biomolécules normales et pathologiques

5 Tampere University Hospital

Abstract : 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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Complete list of metadatas

https://hal-univ-evry.archives-ouvertes.fr/hal-02321460
Contributor : Olek Maciejak <>
Submitted on : Monday, October 21, 2019 - 11:36:46 AM
Last modification on : Tuesday, October 22, 2019 - 5:45:15 PM

Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies

Links full text

Identifiers

Collections

Citation

Export

Metrics

21

Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies

Links full text

Identifiers

Collections

Citation

Export

Share

Metrics

21