Expression of bovine myf5 induces ectopic skeletal muscle formation in transgenic mice.
myf5 is one of a family of four myogenic determination genes that control skeletal muscle differentiation. To study the role of myf5 in vivo, we generated transgenic mice harboring the bovine homolog, bmyf, under control of the murine sarcoma virus promoter. Ectopic expression of the full-length bmyf transgene was detected in brain and heart tissue samples of F1 progeny from transgenic founder mice. Ectopic bmyf expression activated endogenous skeletal myogenic determination genes in the hearts and brains of transgenic animals. Incomplete skeletal myogenesis in most hearts gave rise to cardiomegaly and focal areas of cardiomyopathy. In brains in which ectopic expression led to a more complete myogenesis, focal areas of multinucleated, striated myotubes containing actin, desmin, and myosin were observed. These unexpected results show that myf5 can initiate myogenic differentiation in vivo, supporting the hypothesis that myf5 is responsible for determination of cells to the myogenic lineage in normal embryogenesis.
Santerre
R F
RF
Biotechnology Research, Eli Lilly and Company, Indianapolis, Indiana 46285.
Bales
K R
KR
Janney
M J
MJ
Hannon
K
K
Fisher
L F
LF
Bailey
C S
CS
Morris
J
J
Ivarie
R
R
Smith
C K
CK
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D051787:Myogenic Regulatory Factor 5; D015534:Trans-Activators
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D015534:Trans-Activators; D004247:DNA