title: Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart.
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.
authors.affiliation: Division of Molecular Cardiovascular Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Jones
authors.forename: I L
authors.initials: IL
authors.lastname: Grupp
authors.forename: T
authors.initials: T
authors.lastname: Doetschman
authors.forename: G
authors.initials: G
authors.lastname: Grupp
authors.forename: H
authors.initials: H
authors.lastname: Osinska
authors.forename: T E
authors.initials: TE
authors.lastname: Hewett
authors.forename: G
authors.initials: G
authors.lastname: Boivin
authors.forename: J
authors.initials: J
authors.lastname: Gulick
authors.forename: W A
authors.initials: WA
authors.lastname: Ng
authors.forename: J
authors.initials: J
authors.lastname: Robbins
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018628:Gene Dosage; D018390:Gene Targeting; D006321:Heart / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000235:genetics*; D016277:Ventricular Function, Left
chemical_list: D018995:Myosin Heavy Chains