| First Author | Blanchard EM | Year | 1997 |
| Journal | Circ Res | Volume | 81 |
| Issue | 6 | Pages | 1005-10 |
| PubMed ID | 9400381 | Mgi Jnum | J:44952 |
| Mgi Id | MGI:1101530 | Doi | 10.1161/01.res.81.6.1005 |
| Citation | Blanchard EM, et al. (1997) Targeted ablation of the murine alpha-tropomyosin gene. Circ Res 81(6):1005-10 |
| abstractText | We created a mouse that lacks a functional alpha-tropomyosin gene using gene target-ing in embryonic stem cells and blastocyst-mediated transgenesis. Homozygous alpha-tropomyosin knockout mice die between embryonic day 9.5 and 13.5 and lack alpha-tropo-myosin mRNA. Heterozygous alpha-tropomyosin knockout mice have approximately 50% as much cardiac alpha-tropomyosin mRNA as wild-type littermates but similar alpha-tropomyosin protein levels. Cardiac gross morphology, histology, and function (assessed by working heart preparations) of heterozygous alpha-tropomyosin knockout and wild-type mice were indistinguishable. Mechanical performance of skinned papillary muscle strips derived from mutant and wild-type hearts also revealed no differences. We conclude that haploinsufficiency of the alpha-tropomyosin gene produces little or no change in cardiac function or structure, whereas total alpha-tropomyosin deficiency is incompatible with life. These findings imply that in heterozygotes there is a regulatory mechanism that maintains the level of myofibrillar tropomyosin despite the reduction in alpha-tropomyosin mRNA. |
