Murine phosphatidylserine-specific phospholipase A1 (Ps-pla1) maps to Chromosome 16 but is distinct from the lpd (lipid defect) locus

We have previously generated a mouse transgenic line with an insertional mu tation designated lpd that demonstrates a phenotype of hypertriglyceridemia and fatty liver. Since the recently identified phosphatidylserine-specific phospholipase Al (PS-PLA1) demonstrates significant homology to triglyceri de lipases, we reasoned that the mouse Ps-pla1 gene may be the disrupted ge ne within the lpd locus. Using a rat PS-PLA1 cDNA sequence to search the ES T database, we identified a mouse EST homolog AA839424. Sequencing analysis of AA839424 revealed a putative Ps-pla1 protein of 456 amino acids with ex tensive over all structural conservation with human and rat PS-PLA1 and wit h triglyceride lipases. Conserved sequences in Ps-pla1 include a lipase con sensus sequences GxSxG, a catalytic triad, and eight of the ten conserved c ysteine residues that are required for tertiary structure. Mouse Ps-pla1 ca rries a phosphatidylserine-binding motif that is absent in all triglyceride lipases. Using a mouse whole-genome radiation hybrid (WG-RH) mapping panel (T31), we mapped mouse Ps-pla1 to Chromosome (Chr) 16 between genetic mark ers D16Mir194 and D16Mit38, which is 17.1 cM centromeric to the lpd locus. On the basis of chromosome location, we conclude that Ps-pla1 and lpd are d istinct genes in lipid metabolism.