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Molecular and Cellular Biology, May 2007, p. 3327-3336, Vol. 27, No. 9
0270-7306/07/$08.00+0     doi:10.1128/MCB.01527-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Developmental and Metabolic Effects of Disruption of the Mouse CTP:Phosphoethanolamine Cytidylyltransferase Gene (Pcyt2){triangledown}

Morgan D. Fullerton, Fatima Hakimuddin, and Marica Bakovic*

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada

Received 16 August 2006/ Returned for modification 18 September 2006/ Accepted 8 February 2007

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. [14C]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.

* Corresponding author. Mailing address: Animal Science and Nutrition Building, Room 346, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Phone: (519) 824-4120, ext. 53764. Fax: (519) 763-5902. E-mail: mbakovic{at}uoguelph.ca

{triangledown} Published ahead of print on 26 February 2007.

Molecular and Cellular Biology, May 2007, p. 3327-3336, Vol. 27, No. 9
0270-7306/07/$08.00+0     doi:10.1128/MCB.01527-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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