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Volume 271, Number 37, Issue of September 13, 1996 pp. 22647-22656
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Structure and Expression of the Murine Muscle Adenylosuccinate Synthetase Gene

(Received for publication, March 11, 1996, and in revised form, May 31, 1996)

Amy L. Lewis , Oivin M. Guicherit ^§ , Surjit K. Datta ^§ , Gerri R. Hanten ^§ and Rodney E. Kellems ^§

From ^§ The Verna and Marrs McLean Department of Biochemistry and the  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

A muscle-specific isoform of adenylosuccinate synthetase (AdSS1, EC) is one of three enzymes that constitute the purine nucleotide cycle, a muscle-specific metabolic cycle. Previously, we showed that the muscle Adss1 gene was highly expressed in both skeletal muscle and heart of the adult mouse. Here we have shown that the Adss1 gene is initially activated early in embryonic development in skeletal muscle and heart precursors and is subsequently up-regulated perinatally. The earliest detectable gene expression corresponds with the establishment of the first myogenic and cardiac lineages. To allow identification of the genetic signals controlling this developmental pattern of expression, the Adss1 gene was cloned and its structure determined. Transgenic analysis has shown that 1.9 kilobase pairs of 5 flank can activate expression in skeletal muscle progenitors and direct enhanced expression to adult cardiac muscle. Sequence analysis of the promoter and 5 flanking region revealed the presence of numerous potential muscle-specific cis-regulatory elements.

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