Induction of [beta]mhc transgene in overloaded skeletal muscle is
not eliminated by mutation of conserved elements.
Tsika, Gretchen L., Jennifer L. Wiedenman, Liying Gao, John J.
McCarthy, Katrina Sheriff-Carter, Ilia D. Rivera-Rivera, and Richard
W. Tsika.
Molecular and Integrative Physiology, University of Illinois,
Urbana-Champaign, Illinois 61801
APStracts 3:0175C, 1996.
Mechnical overload leads to hypertrophy, increased type I fiber
composition and beta-myosin heavy chain ([beta]MHC) induction in the
fast-twitch plantaris muscle. To better understand the mechanism(s)
involved in [beta]MHC induction, we have examined inducible
expression of transgenes carrying the simultaneous mutation of three
DNA regulatory subregions (M-CAT, C-rich, and [beta]e3) in the
context of either a 5600 bp ([beta]5.6mut3) or 600 bp ([beta]0.6mut3)
[beta]MHC promoter in overloaded plantaris muscles of transgenic
mice. Protein extract from mechanically overloaded plantaris muscle
of mice harboring either mutant transgene [beta]5.6mut3 or
[beta]0.6mut3 showed an unexpected 2.8 to 4.5 fold increase in
chloramphenicol acetyltransferase (CAT) specific activity relative to
their respective controls. Similar results were obtained with wild
type (wt) [beta]MHC transgenes ([beta]5.6wt, [beta]0.6wt).
Histochemical staining for both mATPase and CAT activity, and CAT
immunohistochemistry revealed a striking increase in type I fibers
and that CAT expression was restricted to these fibers in overloaded
plantaris muscle of [beta]5.6mut3 transgenic mice. Our transgenic
data suggest that [beta]MHC transgenes, and perhaps the endogenous
[beta]MHC gene, are induced by mechanical overload via a mechanism(s)
which does not exclusively require the M-CAT, C-rich or [beta]e3
subregions.
Received 29 February 1996; accepted in final form 24 May 1996.
APS Manuscript Number C111-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96