%0 Journal Article %T Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies %+ Généthon %+ Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE) %+ Folkhälsan Research Center %+ Structure et activité des biomolécules normales et pathologiques (SABNP) %+ Tampere University Hospital %A Charton, Karine %A Danièle, Nathalie %A Vihola, Anna %A Roudaut, Carinne %A Gicquel, Evelyne %A Monjaret, François %A Couturier-Tarrade, Anne %A Sarparanta, Jaakko %A Udd, Bjarne %A Richard, Isabelle %< avec comité de lecture %@ 0964-6906 %J Human Molecular Genetics %I Oxford University Press (OUP) %V 19 %N 23 %P 4608-4624 %8 2010-12-01 %D 2010 %R 10.1093/hmg/ddq388 %K Mutation %K Calpain %K Mice %K Connectin %Z Life Sciences [q-bio]Journal articles %X The dominant tibial muscular dystrophy (TMD) and recessive limb-girdle muscular dystrophy 2J are allelicdisorders caused by mutations in the C-terminus of titin, a giant sarcomeric protein. Both clinical presentationswere initially identified in a large Finnish family and linked to a founder mutation (FINmaj). To furtherunderstand the physiopathology of these two diseases, we generated a mouse model carrying the FINmajmutation. In heterozygous mice, dystrophic myopathology appears late at 9 months of age in few distalmuscles. In homozygous (HO) mice, the first signs appear in the Soleus at 1 month of age and extend tomost muscles at 6 months of age. Interestingly, the heart is also severely affected in HO mice. The mutationleads to the loss of the very C-terminal end of titin and to a secondary deficiency of calpain 3, a partner oftitin. 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. %G English %L hal-02321460 %U https://univ-evry.hal.science/hal-02321460 %~ INSERM %~ CEA %~ CNRS %~ UNIV-CERGY %~ UNIV-EVRY %~ INC-CNRS %~ SABNP %~ LAMBE %~ INTEGRARE %~ UNIV-PARIS-SACLAY %~ GS-HEALTH-DRUG-SCIENCES