A mouse model of familial hypertrophic cardiomyopathy.
A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg 403 --> Gln mutation into the alpha cardiac myosin heavy chain (MHC) gene. Homozygous alpha MHC 403/403 mice died 7 days after birth, and sedentary heterozygous alpha MHC 403/+ mice survived for 1 year. Cardiac histopathology and dysfunction in the alpha MHC 403/+ mice resembled human FHC. Cardiac dysfunction preceded histopathologic changes, and myocyte disarray, hypertrophy, and fibrosis increased with age. Young male alpha MHC 403/+ mice showed more evidence of disease than did their female counterparts. Preliminary results suggested that exercise capacity may have been compromised in the alpha MHC 403/+ mice. This mouse model may help to define the natural history of FHC.
Geisterfer-Lowrance
A A
AA
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Christe
M
M
Conner
D A
DA
Ingwall
J S
JS
Schoen
F J
FJ
Seidman
C E
CE
Seidman
J G
JG
D000818:Animals; D001483:Base Sequence; D002302:Cardiac Output; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D006321:Heart / Q000503:physiopathology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics*; D005082:Physical Exertion; D012727:Sex Characteristics; D016277:Ventricular Function, Left
D018995:Myosin Heavy Chains