IN-VITRO AND IN-VIVO ANALYSIS OF MURINE LIPOPROTEIN-LIPASE GENE PROMOTER - TISSUE-SPECIFIC EXPRESSION

Lipoprotein lipase, an enzyme of central importance to lipid metabolis m, is most abundant in adipose tissues, cardiac and skeletal muscle, a nd portions of the brain. The current work examined the murine lipopro tein lipase promoter using transient transfection, gel-retention analy ses, and transgenic mice. Maximum expression of the luciferase reporte r gene in transfected cells was observed with -101 bp of the promoter. Nuclear extracts from tissues expressing lipoprotein lipase contained DNA binding proteins that recognize the CCAAT box (-64 bp) and an oct amer motif (-46 bp); this combination of factors was absent in nonexpr essing tissues. Transgenic mice from three of five founders prepared w ith -1,824-bp promoter constructs expressed the luciferase reporter ge ne at highest levels in brown adipose tissue and brain. These findings suggest that the -1,824-bp promoter region contains sequence elements responsible for the tissue-specific transcription of lipoprotein lipa se in vivo.