RGD Reference Report - Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin. - Rat Genome Database

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Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin.

Authors: Kumar, A  Crawford, K  Close, L  Madison, M  Lorenz, J  Doetschman, T  Pawlowski, S  Duffy, J  Neumann, J  Robbins, J  Boivin, GP  O'Toole, BA  Lessard, JL 
Citation: Kumar A, etal., Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4406-11.
RGD ID: 1559159
Pubmed: PMID:9114002   (View Abstract at PubMed)
PMCID: PMC20735   (View Article at PubMed Central)

The muscle actins in higher vertebrates display highly conserved amino acid sequences, yet they show distinct expression patterns. Thus, cardiac alpha-actin, skeletal alpha-actin, vascular smooth muscle alpha-actin, and enteric smooth muscle gamma-actin comprise the major actins in their respective tissues. To assess the functional and developmental significance of cardiac alpha-actin, the murine (129/SvJ) cardiac alpha-actin gene was disrupted by homologous recombination. The majority ( approximately 56%) of the mice lacking cardiac alpha-actin do not survive to term, and the remainder generally die within 2 weeks of birth. Increased expression of vascular smooth muscle and skeletal alpha-actins is observed in the hearts of newborn homozygous mutants and also heterozygotes but apparently is insufficient to maintain myofibrillar integrity in the homozygous mutants. Mice lacking cardiac alpha-actin can be rescued to adulthood by the ectopic expression of enteric smooth muscle gamma-actin using the cardiac alpha-myosin heavy chain promoter. However, the hearts of such rescued cardiac alpha-actin-deficient mice are extremely hypodynamic, considerably enlarged, and hypertrophied. Furthermore, the transgenically expressed enteric smooth muscle gamma-actin reduces cardiac contractility in wild-type and heterozygous mice. These results demonstrate that alterations in actin composition in the fetal and adult heart are associated with severe structural and functional perturbations.

Objects referenced in this article
Gene Actc1 actin, alpha, cardiac muscle 1 Mus musculus

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