Biomaterial Database

Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. 2005

Takuro Arimura, and Anne Helbling-Leclerc, and Catherine Massart, and Shaida Varnous, and Florence Niel, and Emmanuelle Lacène, and Yves Fromes, and Marcel Toussaint, and Anne-Marie Mura, and Dagmar I Keller, and Helge Amthor, and Richard Isnard, and Marie Malissen, and Ketty Schwartz, and Gisèle Bonne

Inserm UR582, Institut de Myologie, GH Pitié-Salpêtrière, Paris, France.

Laminopathies are a group of disorders caused by mutations in the LMNA gene encoding A-type lamins, components of the nuclear lamina. Three of these disorders affect specifically the skeletal and/or cardiac muscles, and their pathogenic mechanisms are still unknown. We chose the LMNA H222P missense mutation identified in a family with autosomal dominant Emery-Dreifuss muscular dystrophy, one of the striated muscle-specific laminopathies, to create a faithful mouse model of this type of laminopathy. The mutant mice exhibit overtly normal embryonic development and sexual maturity. At adulthood, male homozygous mice display reduced locomotion activity with abnormal stiff walking posture and all of them die by 9 months of age. As for cardiac phenotype, they develop chamber dilation and hypokinesia with conduction defects. These abnormal skeletal and cardiac features were also observed in the female homozygous mice but with a later-onset than in males. Histopathological analysis of the mice revealed muscle degeneration with fibrosis associated with dislocation of heterochromatin and activation of Smad signalling in heart and skeletal muscles. These results demonstrate that LmnaH222P/H222P mice represent a good model for studying laminopathies affecting striated muscles as they develop a dystrophic condition of both skeletal and cardiac muscles similar to the human diseases.

UI	MeSH Term	Description	Entries
D009137	Muscular Dystrophy, Animal	MUSCULAR DYSTROPHY that occurs in VERTEBRATE animals.	Animal Muscular Dystrophies,Animal Muscular Dystrophy,Dystrophies, Animal Muscular,Dystrophy, Animal Muscular,Muscular Dystrophies, Animal
D002311	Cardiomyopathy, Dilated	A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.	Cardiomyopathy, Congestive,Congestive Cardiomyopathy,Dilated Cardiomyopathy,Cardiomyopathy, Dilated, 1a,Cardiomyopathy, Dilated, Autosomal Recessive,Cardiomyopathy, Dilated, CMD1A,Cardiomyopathy, Dilated, LMNA,Cardiomyopathy, Dilated, With Conduction Defect 1,Cardiomyopathy, Dilated, with Conduction Deffect1,Cardiomyopathy, Familial Idiopathic,Cardiomyopathy, Idiopathic Dilated,Cardiomyopathies, Congestive,Cardiomyopathies, Dilated,Cardiomyopathies, Familial Idiopathic,Cardiomyopathies, Idiopathic Dilated,Congestive Cardiomyopathies,Dilated Cardiomyopathies,Dilated Cardiomyopathies, Idiopathic,Dilated Cardiomyopathy, Idiopathic,Familial Idiopathic Cardiomyopathies,Familial Idiopathic Cardiomyopathy,Idiopathic Cardiomyopathies, Familial,Idiopathic Cardiomyopathy, Familial,Idiopathic Dilated Cardiomyopathies,Idiopathic Dilated Cardiomyopathy
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D020125	Mutation, Missense	A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)	Missense Mutation,Missense Mutations,Mutations, Missense
D020389	Muscular Dystrophy, Emery-Dreifuss	A heterogenous group of inherited muscular dystrophy without the involvement of nervous system. The disease is characterized by MUSCULAR ATROPHY; MUSCLE WEAKNESS; CONTRACTURE of the elbows; ACHILLES TENDON; and posterior cervical muscles; with or without cardiac features. There are several INHERITANCE PATTERNS including X-linked (X CHROMOSOME), autosomal dominant (for LMNA-associated type see AUTOSOMAL EMERY-DREIFUSS MUSCULAR DYSTROPHY), and autosomal recessive gene mutations.	Emery-Dreifuss Syndrome,Autosomal Recessive Emery-Dreifuss Muscular Dystrophy,Emery-Dreifuss Muscular Dystrophy,Emery-Dreifuss Muscular Dystrophy, Autosomal Recessive,Emery-Dreifuss Type Muscular Dystrophy,Muscular Dystrophy, Emery-Dreifuss Type,Muscular Dystrophy, Emery-Dreifuss, Autosomal Recessive,Muscular Dystrophy, Scapuloperoneal,Scapuloperoneal Muscular Dystrophy,Scapuloperoneal Myopathy, MYH7-Related,Autosomal Recessive Emery Dreifuss Muscular Dystrophy,Emery Dreifuss Muscular Dystrophy,Emery Dreifuss Muscular Dystrophy, Autosomal Recessive,Emery Dreifuss Syndrome,MYH7-Related Scapuloperoneal Myopathy,Muscular Dystrophy, Emery Dreifuss,Myopathy, MYH7-Related Scapuloperoneal,Scapuloperoneal Myopathy, MYH7 Related
D034904	Lamin Type A	A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.	Lamin A,Lamin A-C,Type A Lamins,Lamin A C,Lamins, Type A