Placental Thrombosis and Spontaneous Fetal Death in Mice Deficient in Ethanolamine Kinase 2

Abstract

Ethanolamine kinase catalyzes the first step in the CDP-ethanolamine pathway for the formation of the major membrane phospholipid phosphatidylethanolamine (PtdEtn). In this work, the predicted Etnk2 cDNA was established as a soluble protein with ethanolamine-specific kinase activity that was most highly expressed in liver. Mice with an inactivated Etnk2 gene were derived, and its absence reduced the rate of PtdEtn synthesis from exogenous ethanolamine in hepatocytes. PtdEtn is a major precursor to phosphatidylcholine in liver; however, Etnk2 ؊/؊ mice did not have reduced amounts of either PtdEtn or phosphatidylcholine or an altered phospholipid molecular species distribution. The knock-out animals were able to adapt to a choline-deficient diet. The Etnk2 ؊/؊ mice exhibited a maternalspecific intrauterine growth retardation phenotype that resulted in a 33% reduction in litter size and frequent perinatal death. Histological analysis of pregnant Etnk2 ؊/؊ females showed that fetal development failed at the late stage of pregnancy in a significant percentage of embryos because of the appearance of extensive placental thrombosis. These results illustrate a non-redundant role for EtnK2 expression in regulating placental hemostasis.

Comparative genomics and evolution of eukaryotic phospholipid biosynthesis

“…However, work on the Drosphila easily shocked gene pointed to the reality of ethanolamine specific enzymes as well as to their potentially significant physiological role [67]. Subsequent work demonstrated the existence of two mammalian EK enzymes, EK1 and EK2 [68,69]. Mice deficient in EK2 showed reproductive defects due to extensive placental thrombosis [69].…”

“…Subsequent work demonstrated the existence of two mammalian EK enzymes, EK1 and EK2 [68,69]. Mice deficient in EK2 showed reproductive defects due to extensive placental thrombosis [69]. S.…”

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

“…In addition, a cDNA encoding a human ethanolamine kinase that lacks significant choline kinase activity has also been cloned (124). Mice lacking the ethanolamine-specific kinase have been generated (125). In these mice, the PE content of the liver was not decreased but litter size was reduced and ?20% of the pups died perinatally.…”

AP4 Transcription Factor Binding Site is a Repressor Element in ek2 Promoter of Human Liver Carcinoma Cell Line, HepG2

“…These studies therefore proved that EK1 and EK2 are indeed different, despite their similarities in sequence. Ek2 knocked out mice did not affect liver phospholipid metabolism, neural development, or testicular function but instead, have major effects on maternal-specific failure to support late embryonic development because of the development of placental thrombosis, which resulted in 33% reduced litter size (Tian et al 2006).…”

“…In situations when choline is deficient, EK2 is important in supplying PtdEtn to prevent liver malfunction (Tian et al 2006;Walkey et al 1998). EK2 was reported to be involved in testicular maturation as suggested by its pattern of expression in developing mouse testes (Hurley et al 2004).…”