STRUCTURE AND EXPRESSION OF THE MURINE MUSCLE ADENYLOSUCCINATE SYNTHETASE GENE

A muscle-specific isoform of adenylosuccinate synthetase (AdSS1, EC 6. 3.4.4) is one of three enzymes that constitute the purine nucleotide c ycle, a muscle-specific metabolic cycle. Previously, we showed that th e muscle Adss1 gene was highly expressed in both skeletal muscle and h eart of the adult mouse. Here we have shown that the Adss1 gene is ini tially activated early in embryonic development in skeletal muscle and heart precursors and is subsequently up regulated perinatally. The ea rliest detectable gene expression corresponds with the establishment o f the first myogenic and cardiac lineages. To allow identification of the genetic signals controlling this developmental pattern of expressi on, the Adss1 gene was cloned and its structure determined. Transgenic analysis has shown that 1.9 kilobase pairs of 5' flank can activate e xpression in skeletal muscle progenitors and direct enhanced expressio n to adult cardiac muscle. Sequence analysis of the promoter and 5' fl anking region revealed the presence of numerous potential muscle-speci fic cis-regulatory elements.