Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart.
J Clin Invest
; 98(8): 1906-17, 1996 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-8878443
ABSTRACT
The alpha-myosin heavy chain (alpha-MyHC) is the major contractile protein expressed in the myocardium of adult mice. We have produced mice carrying a null mutation of alpha-MyHC by homologous recombination in murine ES cells. Homozygous null animals die between 11 and 12 d in utero of gross heart defects, while alpha-MyHC+/- heterozygotes survive and appear externally normal. The presence of a single functional alpha-MyHC+ allele in heterozygous animals results in reduced levels of the transcript and protein as well as fibrosis and alterations in sarcomeric structure. Examination of heart function using a working heart preparation revealed severe impairment of both contractility and relaxation in a subset of the alpha-MyHC+/- animals. Thus, two alpha-MyHC+ alleles are necessary for normal cardiac development, and hemizygosity for the normal allele can result in altered cardiac function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dosagem de Genes
/
Cadeias Pesadas de Miosina
/
Coração
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos