Decreased m-creatine kinase gene expression in mechanically
overloaded skeletal muscle of transgenic mice.
Tsika, Richard W., Stephen D. Hauschka, and Liying Gao.
Department of Physiology, University of Illinois, Urbana-Champaign,
Illinois 61801, and Biochemistry Department, University of
Washington, Seattle, Washington 98195
APStracts 2:0129C, 1995.
The molecular pathways and regulatory molecules which underlie changes
in gene transcription during mechanical overload of skeletal muscle
remain obscure. To better understand this process we have examined
mouse muscle creatine kinase (MCK) gene expression in mechanically
overloaded plantaris (OP) muscle of transgenic and nontransgenic
mice. Northern blot analysis revealed that endogenous MCK specific
mRNA transcripts were decreased 150% in the OP muscles after 6 weeks.
To identify the MCK gene regions involved in the response to
mechanical overload, three different mouse MCKCAT transgenes were
studied by measuring chloramphenicol acetyltransferase activity (CAT
assays) in OP and sham operated (CP) muscles. Mouse lines carrying
(+enh206)-117MCKCAT and -1256MCKCAT transgenes exhibited 30 and 40%
lower CAT levels, whereas two mouse lines carrying -3300MCKCAT
transgenes exhibited average decreases of 430%. Nearly identical
results, including measurements of exogenous CAT mRNA, were obtained
2 days postoverload. Six weeks or 2 days of mechanical overload lead
to an average decrease in MM-CK isoprotein of 140%. These data
provide evidence that mechanical overload induces changes in MCK gene
expression which appear to be regulated by at least two portions of
the MCK gene: the 206 base pair 5' enhancer, and the (-3300 to -1257)
region.
Received 3 October 1994; accepted in final form 2 March 1995.
APS Manuscript Number C598-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 March 1995.