Affiliation:
1. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada
Abstract
ABSTRACT
The CDP-ethanolamine pathway is responsible for the de novo biosynthesis of ethanolamine phospholipids, where CDP-ethanolamine is coupled with diacylglycerols to form phosphatidylethanolamine. We have disrupted the mouse gene encoding CTP:phosphoethanolamine cytidylyltransferase, Pcyt2, the main regulatory enzyme in this pathway. Intercrossings of
Pcyt2
+/
−
animals resulted in small litter sizes and unexpected Mendelian frequencies, with no null mice genotyped. The
Pcyt2
−
/
−
embryos die after implantation, prior to embryonic day 8.5. Examination of mRNA expression, protein content, and enzyme activity in
Pcyt2
+/
−
animals revealed the anticipated 50% decrease due to the gene dosage effect but rather a 20 to 35% decrease. [
14
C]ethanolamine radiolabeling of hepatocytes, liver, heart, and brain corroborated
Pcyt2
gene expression and activity data and showed a decreased rate of phosphatidylethanolamine biosynthesis in heterozygotes. Total phospholipid content was maintained in
Pcyt2
+/
−
tissues; however, this was not due to compensatory increases in the decarboxylation of phosphatidylserine. These results establish the necessity of
Pcyt2
for murine development and demonstrate that a single
Pcyt2
allele in heterozygotes can maintain phospholipid homeostasis.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
89 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献