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A Novel Mouse Model with Targeted and Inducible Deletion of Intestinal CTP:Phosphocholine Cytidylyltransferase α
Author(s) -
Kennelly John Paul,
Veen Jelske,
Nelson Randy,
Silva Robin,
Kelly Karen,
Leonard KellyAnn,
Wan Sereana,
Jacobs René
Publication year - 2016
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.30.1_supplement.1134.6
Subject(s) - phosphocholine , lipid metabolism , very low density lipoprotein , lipoprotein , phospholipid , biochemistry , chylomicron , phosphatidylcholine , biology , chemistry , medicine , endocrinology , cholesterol , membrane
Phosphatidylcholine (PC) is the primary phospholipid in mammalian cell membranes, bile, lipid droplets and plasma lipoproteins, and also serves as a precursor for signalling molecules. PC is produced from choline by the CDP‐choline (Kennedy) pathway in all nucleated cells, and the enzyme CTP: phosphocholine Cytidylyltransferase (CT) regulates flux through the pathway. CTα is the predominant isoform in most major tissues, including the liver and intestine. CTα is an important regulator of very‐low density lipoprotein (VLDL) and high‐density lipoprotein (HDL) metabolism the liver. CT also functions to maintain the structural integrity of membranes and to incorporate fatty acids into lipid droplets to avoid cell toxicity, roles which may be particularly important in the intestine which sees large quantities of dietary lipid. However, our understanding of the role of CT and PC in intestinal lipid and lipoprotein metabolism is incomplete. To determine the functional importance of CTα in regulating intestinal lipid and lipoprotein metabolism in vivo , we have generated mice in which we can induce partial (CTα −/+ ) or complete (CTα −/− ) deletion of CTα using a tamoxifen‐inducible Cre‐Lox system. Preliminary data suggest that CTα +/− mice have altered levels of PC in the intestine and impaired chylomicron secretion as compared to controls with normal intestinal CTα activity. Surprisingly, plasma triglyceride was also increased in CTα +/− mice. Future studies will investigate the compensatory mechanisms in the intestine in response to impaired PC supply. Support or Funding Information NSERC and CIHR