MOLECULAR-CLONING AND CHROMOSOMAL ASSIGNMENT OF THE HUMAN HOMOLOG OF THE RAT CGMP-INHIBITED PHOSPHODIESTERASE-1 (PDE3A) - A GENE INVOLVED IN FAT-METABOLISM LOCATED AT 11P15.1

We have cloned the coding region of a human gene, whose predicted amin o acid sequence shows 88% homology and higher correspondence in functi onal domains to the rat cGMP inhibited phosphodiesterase gene (PDE3A). In concordance with the expression data of the rat PDE3A gene, a 5.3- kb transcript of the human cGMP-inhibited phosphodiesterase gene is sh own in Northern blot analysis to be highly expressed in adipose tissue . In addition, weaker expression is seen in pancreas, skeletal muscle, Liver, placenta, and heart. cDNA clones from the homologue mouse gene were isolated and sequenced spanning a highly conserved region coding for a C-terminal located catalytic core region of this enzyme family. Using a genomic cosmid clone of human PDE3A for fluorescence in situ hybridization, the gene was mapped to chromosomal region 11p15 and reg ionally sublocalized by PCR on a human-hamster somatic hybrid-cell map ping panel to 11p15.1-p2. Based on comparative linkage data in mouse a nd rat this chromosomal location is suggested to contain genes involve d in complex diseases like obesity and diabetes mellitus type II. Ther efore, a possible involvement of the human PDE3A gene in these polygen ic traits is discussed, taking into account the prominent role of the rat PDE3A gene product in the antilipolytic action of insulin in adipo cytes. (C) 1996 Academic Press Inc.