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Published April 1, 1992 | Published
Journal Article Open

Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart


Forced expression of the myogenic regulatory gene MyoD in many types of cultured cells initiates their conversion into skeletal muscle. It is not known, however, if MyoD expression serves to activate all or part of the skeletal muscle program in vivo during animal development, nor is it known how limiting the influences of cellular environment may be on the regulatory effects of MyoD. To begin to address these issues, we have produced transgenic mice which express MyoD in developing heart, where neither MyoD nor its three close relatives—myogenin, Myf-5, and MRF4/herculin/Myf-6—are normally expressed. The resulting gross phenotype in offspring from multiple, independent transgenic founders includes abnormal heart morphology and ultimately leads to death. At the molecular level, affected hearts exhibit activation of skeletal muscle-specific regulatory as well as structural genes. We conclude that MyoD is able to initiate the program that leads to skeletal muscle differentiation during mouse development, even in the presence of the ongoing cardiac differentiation program. Thus, targeted misexpression of this tissue-specific regulator during mammalian embryogenesis can activate, either directly or indirectly, a diverse set of genes normally restricted to a different cell lineage and a different cellular environment.

Additional Information

© 1992 The Company of Biologists Limited. Accepted 9 January 1992. We thank J. Buskin, A. Lassar, E. Olson, and J. Johnson for plasmids; T. Wilkie for heart cDNA; D. Laird, S. Schiaffino, J. Leger, and Z. Kaprielian for antibodies; J. Manning, J. Dausman, J. Johnson, S. T. Trivedi, and J.-P. Revel for assistance; L. Kedes, D. Anderson, N. Davidson, and P. Sternberg for comments; and the Wold group for their help and insights. J. H. M. was supported by a NSF Graduate Fellowship and by the NIH. This work was funded by grants from the Lucille P. Markey Charitable Trust, the Muscular Dystrophy Association, and the NIH to B. W. and a grant from the NIH to J. B. M. J. B. M. is an Established Investigator of the American Heart Association.

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