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Published August 1989 | Published
Journal Article Open

Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice


Muscle creatine kinase (MCK) is expressed at high levels only in skeletal and cardiac muscle tissues. Previous in vitro transfection studies of skeletal muscle myoblasts and fibroblasts had identified two MCK enhancer elements and one proximal promoter element, each of which exhibited expression only in differentiated skeletal muscle. In this study, we have identified several regions of the mouse MCK gene that are responsible for tissue-specific expression in transgenic mice. A fusion gene containing 3,300 nucleotides of MCK 5' sequence exhibited chloramphenicol acetyltransferase activity levels that were more than 10(4)-fold higher in skeletal muscle than in other, nonmuscle tissues such as kidney, liver, and spleen. Expression in cardiac muscle was also greater than in these nonmuscle tissues by 2 to 3 orders of magnitude. Progressive 5' deletions from nucleotide -3300 resulted in reduced expression of the transgene, and one of these resulted in a preferential decrease in expression in cardiac tissue relative to that in skeletal muscle. Of the two enhancer sequences analyzed, only one directed high-level expression in both skeletal and cardiac muscle. The other enhancer activated expression only in skeletal muscle. These data reveal a complex set of cis-acting sequences that have differential effects on MCK expression in skeletal and cardiac muscle.

Additional Information

© 1989 by the American Society for Microbiology. Received 28 November 1988;accepted 24 April 1989. We thank Cyndy Gartside, Tom Balestreri, and Dave Clary for excellent technical assistance, Jessie Dausman for training in microinjection and embryo transfer, Tom Wilkie for generating some of the transgenic mice, and Jean Buskin, Paul Mueller, Melvin Simon, and Tom Wilkie for critical reading of the manuscript. This work was supported by Public Health Service grants AR18860 and HL39070 from the National Institutes of Health and a grant from the Muscular Dystrophy Association to S.D.H., by Public Health Service grant GM35526 from the National Institutes of Health, by a grant from the Rita Allen Foundation, and by Public Health Service biomedical research grant RR07003 to B.J.W. and training grant HD07183 to J.E.J., both from the National Institutes of Health.

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August 22, 2023
October 23, 2023