Targeted ablation of the murine α-tropomyosin gene

EM Blanchard, K Iizuka, M Christe, DA Conner… - Circulation …, 1997 - Am Heart Assoc
EM Blanchard, K Iizuka, M Christe, DA Conner, A Geisterfer-Lowrance, FJ Schoen…
Circulation research, 1997Am Heart Assoc
We created a mouse that lacks a functional α-tropomyosin gene using gene targeting in
embryonic stem cells and blastocyst-mediated transgenesis. Homozygous α-tropomyosin
“knockout” mice die between embryonic day 9.5 and 13.5 and lack α-tropomyosin mRNA.
Heterozygous α-tropomyosin knockout mice have≈ 50% as much cardiac α-tropomyosin
mRNA as wild-type littermates but similar α-tropomyosin protein levels. Cardiac gross
morphology, histology, and function (assessed by working heart preparations) of …
Abstract
We created a mouse that lacks a functional α-tropomyosin gene using gene targeting in embryonic stem cells and blastocyst-mediated transgenesis. Homozygous α-tropomyosin “knockout” mice die between embryonic day 9.5 and 13.5 and lack α-tropomyosin mRNA. Heterozygous α-tropomyosin knockout mice have ≈50% as much cardiac α-tropomyosin mRNA as wild-type littermates but similar α-tropomyosin protein levels. Cardiac gross morphology, histology, and function (assessed by working heart preparations) of heterozygous α-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 α-tropomyosin gene produces little or no change in cardiac function or structure, whereas total α-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 α-tropomyosin mRNA.
Am Heart Assoc