Muscle specific and inducible expression of 293 base pair [beta]myosin heavy chain promoter in transgenic mice. Wiedenman, Jennifer L., Gretchen L. Tsika, Liying Gao, John J. McCarthy, Ilia D. Rivera-Rivera, Dharmesh Vyas, Katrina Sheriff -Carter, and Richard W. Tsika. Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign, Illinois 61801
APStracts 3:0165R, 1996.
The DNA regulatory element(s) involved in beta-myosin heavy chain ([beta]MHC) induction by the physiological stimulus of mechanical overload have not been identified as yet. To delineate regulatory sequences which are required for mechanical overload induction of the [beta]MHC gene, transgenic mouse lines were generated which harbor transgenes containing serial deletions of the human [beta]MHC promoter to nucleotides -293 ([beta]293), -201 ([beta]201), and -141 ([beta]141) from the transcription start site (+1). Mechanically overloaded adult plantaris and soleus muscles contained an 11 and 1.9 fold increase respectively, in endogenous [beta]MHC specific mRNA transcripts (Northern blot) when compared to sham-operated controls. Expression assays (chloramphenicol acetyltransferase (CAT) specific activity) revealed that only transgene [beta]293 expression was muscle specific in both fetal and adult mice, and was induced in the plantaris (10 to 27 fold) and soleus (2 to 2.5 fold) muscles by mechanical overload. Histochemical staining for myosin adenosinetriphosphatase (mATPase) activity revealed a fiber-type transition of type II to type I in the overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous [beta]MHC gene in response to developmental signals and to the physiological signals generated by mechanical overload in fast- and slow-twitch muscles. 

Received 16 January 1996; accepted in final form 19 April 1996.
APS Manuscript Number R26-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96