Mouse glycosylphosphatidylinositol-specific phospholipase D (Gpld1) characterization

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is an 110-kDa monomeric protein found in the circulation that is capable of degrading the GPI anchor utilized by dozens of cell-surface proteins in the presence of detergent. This protein is relatively abundant (5-10 microgram/ml in human serum), yet its sites of synthesis, gene structure, and overall function are unclear. It is our purpose to use the mouse system to determine its putative roles in lipid transport, pathogen control, and diabetes. We have isolated murine full-length cDNA for GPI-PLD from a pancreatic alpha cell library. The deduced amino acid sequence shows 74% homology to bovine and human GPI-PLD. There is a single structural gene (Gpld1) mapping to mouse Chromosome (Chr) 13, and among nine tissues, liver showed the greatest abundance of GPI-PLD mRNA. Genetic differences in serum GPI-PLD activity were seen among four mouse strains, and no correlation was seen between GPI-PLD activity and circulating levels of high density lipoproteins in these mice. This is the first report of map position and genetic regulation for Gpld1. This information will enable us to further study the expression and function of GPI-PLD in normal and pathological conditions.