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 mutation designated lpd that demonstrates a phenotype of hypertriglyceridemia and fatty liver. Since the recently identified phosphatidylserine-specific phospholipase A1 (PS-PLA1) demonstrates significant homology to triglyceride lipases, we reasoned that the mouse Ps-plaI gene may be the disrupted gene within the lpd locus. Using a rat PS-PLA1 cDNA sequence to search the EST database, we identified a mouse EST homolog AA839424. Sequencing analysis of AA839424 revealed a putative Ps-pla1 protein of 456 amino acids with extensive overall structural conservation with human and rat PS-PLA1 and with triglyceride lipases. Conserved sequences in Ps-pla1 include a lipase consensus sequences GxSxG, a catalytic triad, and eight of the ten conserved cysteine residues that are required for tertiary structure. Mouse Ps-plal carries 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 markers D16Mit194 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 distinct genes in lipid metabolism.
Wen
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Department of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Ontario, Canada. x.wen@utoronto.ca
Stewart
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Skaug
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Wei
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Tsui
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LC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020224:Expressed Sequence Tags; D008049:Lipase / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000378:metabolism*; D010741:Phospholipases A / Q000235:genetics*; D054466:Phospholipases A1; D021101:Radiation Hybrid Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D010718:Phosphatidylserines; D008049:Lipase; C512665:PLA1A protein, human; D010741:Phospholipases A; D054466:Phospholipases A1; C512666:Pla1a protein, mouse; C512667:Pla1a protein, rat