HORMONE-SENSITIVE LIPASE (LIPE) - SEQUENCE-ANALYSIS OF THE 129SV MOUSE LIPE GENE

Hormone-sensitive lipase (Lipe) catalyzes both the release of fatty ac ids from storage triglycerides in adipocytes and the liberation of cho lesterol from cholesterol esters in steroidogenic tissues. Lipe activi ty is regulated in a tissue-, development- and hormone-specific fashio n, the latter in large part by serine phosphorylation. We cloned and s equenced the Lipe gene from the 129Sv strain mouse, including 2.7 kb o f the 5' nontranslated region. The primary transcript of the 129Sv Lip e locus spans 9.6 kb and contains 9 exons. We studied the curious hype rvariable region immediately 5' to the regulatory serine residues by a ligning the peptide and nucleic acid sequences of mouse, human, and ra t Lipe. We propose that much of the variability is attributable to dif ferences in the copy number of a 12-nucleotide repeat that shifts the intron 7 acceptor splice site. Introns 1 and 7 contain B1 elements, wh ich in intron 7 are immediately adjacent to a tetranucleotide repeat. The mouse Lipe promoter region contains numerous potential binding mot ifs for factors implicated in adipose tissue expression and hormone re sponsiveness including adipocyte determination- and differentiation-de pendent factor 1 (ADD1/SREBP1).