| First Author | Kumar A | Year | 1997 |
| Journal | Proc Natl Acad Sci U S A | Volume | 94 |
| Issue | 9 | Pages | 4406-11 |
| PubMed ID | 9114002 | Mgi Jnum | J:40165 |
| Mgi Id | MGI:87509 | Doi | 10.1073/pnas.94.9.4406 |
| Citation | Kumar A, et al. (1997) Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin. Proc Natl Acad Sci U S A 94(9):4406-11 |
| abstractText | 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. |
