Physiological consequences of disruption of mammalian phospholipid biosynthetic genes

• Main Authors: Dennis E. Vance, Jean E. Vance
• Format: Article
• Language: English
• Published: Elsevier 2009-01-01
• Series: Journal of Lipid Research
• Subjects: phosphatidylcholine; phosphatidylethanolamine; phosphatidylserine; choline kinase; CTP:phosphocholine cytidylyltransferase; phosphatidylethanolamine N-methyltransferase
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520306003

By 1959, Eugene Kennedy and coworkers had outlined most pathways of phospholipid biosynthesis. In the next four decades, the emphasis was on enzymology and regulation of these pathways. In the last 12 years, several lines of mice with disrupted genes of phospholipid biosynthesis were generated. From this research, we have learned that embryonic lethality occurs in mice that lack choline kinase (CK) α, CTP:phosphocholine cytidylyltransferase α, CTP:phosphoethanolamine cytidylyltransferase, or phosphatidylserine decarboxylase. Whereas mice that lack CK β are viable but develop hindlimb muscular dystrophy and neonatal bone deformity. Mice that lack CTP:phosphocholine cytidylytransferase β have gonadal dysfunction and defective axon branching. Mice that lack phosphatidylethanolamine N-methyltransferase exhibit no phenotype until fed a choline-deficient diet, which leads to rapid liver failure. Future research should extend our knowledge about the function of these and other enzymes of phospholipid biosynthesis.