| First Author | Semsarian C | Year | 2001 |
| Journal | J Mol Cell Cardiol | Volume | 33 |
| Issue | 11 | Pages | 2055-60 |
| PubMed ID | 11708849 | Mgi Jnum | J:89230 |
| Mgi Id | MGI:3039200 | Doi | 10.1006/jmcc.2001.1466 |
| Citation | Semsarian C, et al. (2001) A polymorphic modifier gene alters the hypertrophic response in a murine model of familial hypertrophic cardiomyopathy. J Mol Cell Cardiol 33(11):2055-60 |
| abstractText | Familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disorder caused by mutationally altered dominant-acting sarcomere proteins, exhibits significant clinical heterogeneity. To determine whether genetic background could influence the expression of this disease, we studied a murine model for this human condition. Hypertrophic responses to the Arg403Gln missense mutation in a cardiac myosin heavy chain gene were compared in 129SvEv (inbred; designated 129SvEv- alpha MHC403/+) and Black Swiss (outbred; designated BSw- alpha MHC403/+) strains. At 30-50 weeks of age all 129SvEv- alpha MHC403/+ showed left ventricular hypertrophy, while left ventricular wall thickness was increased in only half of BSw- alpha MHC403/+ mice demonstrating that a polymorphic modifier gene can determine the hypertrophic response to this dominant-acting sarcomere protein mutation. Further analysis suggests that SJL/J mice bear a recessive allele of this modifier gene that prevents a hypertrophic response to the Arg403Gln missense mutation. We conclude that genetic modifiers in mice, and presumably in man, can alter the hypertrophic response to sarcomere protein gene missense mutations. |
