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Early embryonic lethality caused by disruption of the gene for choline kinase alpha, the first enzyme in phosphatidylcholine biosynthesis
Author(s) -
Wu Gengshu,
Aoyama Chieko,
Young Stephen G.,
Vance Dennis E.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a238-b
Subject(s) - choline kinase , phosphocholine , choline , biology , mutant , phosphatidylcholine , microbiology and biotechnology , biosynthesis , pld2 , biochemistry , phospholipid , enzyme , gene , membrane
Choline kinase alpha (CK‐α) is one of two mammalian choline kinase (CK) enzymes (α and β) that catalyze the phosphorylation of choline to phosphocholine in the biosynthesis of the major membrane phospholipid, phosphatidylcholine (PC). To investigate the specific role of CK‐α we created mice lacking CK‐α with a ES cell line containing an insertional mutation in the gene for CK‐α ( Chka ). Embryos homozygous for the mutant Chka allele were recovered at the blastocyst stage, but not at E7.5, indicating that CK‐α is crucial for the early development of mouse embryos. Heterozygous mutant mice ( Chka +/− ) appeared entirely normal in their embryonic development and gross anatomy and were fertile. Although CK activity was decreased by ~ 30% in the livers and testes of Chka +/− mice, the amount of PC in cells and the levels of other enzymes involved in PC biosynthesis were unaffected. Triacylglycerol and cholesterol ester were elevated ~twofold in the livers whereas neutral lipid profiles in plasma were similar in Chka +/− and wild‐type ( Chka +/+ ) mice. Enhanced levels of choline and attenuated levels of phosphocholine were observed both in liver and in testis from Chka +/− mice. Thus, Chka is an essential gene in mice, but mice do not require full expression of the gene for normal levels of PC in cells. This research was supported by a grant from the Canadian Institutes of Health Research and an NHLBI‐funded Program for Genomics Applications (“BayGenomics,” HL66621, HL66600, and HL66590)