Defining the importance of phosphatidylserine synthase 2 in mice.
Phosphatidylserine synthase 1 (Pss1) and phosphatidylserine synthase 2 (Pss2) produce phosphatidylserine by exchanging serine for the head groups of other phospholipids. Pss1 and Pss2 are structurally similar (approximately 32% amino acid identity) but differ in their substrate specificities, with Pss1 using phosphatidylcholine for the serine exchange reaction and Pss2 using phosphatidylethanolamine. Whether Pss1 and Pss2 are both required for mammalian growth and development is not known, and no data exist on the relative contributions of the two enzymes to serine exchange activities in different tissues. To address those issues and also to define the cell type-specific expression of Pss2, we generated Pss2-deficient mice in which a beta-galactosidase marker is expressed from Pss2 regulatory sequences. Histologic studies of Pss2-deficient mice revealed very high levels of beta-galactosidase expression in Sertoli cells of the testis and high levels of expression in brown fat, neurons, and myometrium. The ability of testis extracts from Pss2-deficient mice to catalyze serine exchange was reduced by more than 95%; reductions of approximately 90% were noted in the brain and liver. However, we found no perturbations in the phospholipid content of any of these tissues. As judged by Northern blots, the expression of Pss1 was not up-regulated in Pss2-deficient cells and tissues. Testis weight was reduced in Pss2-deficient mice, and some of the male mice were infertile. We conclude that Pss2 is responsible for the majority of serine exchange activity in in vitro assays, but a deficiency in this enzyme does not cause perturbations in phospholipid content or severe developmental abnormalities.
D000818:Animals; D015152:Blotting, Northern; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000097:blood; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D019884:Nitrogenous Group Transferases / Q000235:genetics / Q000502:physiology*; D009929:Organ Size; D010718:Phosphatidylserines / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000378:metabolism
D018076:DNA, Complementary; D010718:Phosphatidylserines; D012313:RNA; D005640:Follicle Stimulating Hormone; D019884:Nitrogenous Group Transferases; C111493:Ptdss2 protein, mouse; D001616:beta-Galactosidase