title: Conditional Tek promoter-driven deletion of arginyltransferase in the germ line causes defects in gametogenesis and early embryonic lethality in mice.
abstract: Posttranslational protein arginylation mediated by Ate1 is essential for cardiovascular development, actin cytoskeleton functioning, and cell migration. Ate1 plays a role in the regulation of cytoskeleton and is essential for cardiovascular development and angiogenesis--capillary remodeling driven by in-tissue migration of endothelial cells. To address the role of Ate1 in cytoskeleton-dependent processes and endothelial cell function during development, we produced a conditional mouse knockout with Ate1 deletion driven by Tek endothelial receptor tyrosine kinase promoter expressed in the endothelium and in the germ line. Contrary to expectations, Tek-Ate1 mice were viable and had no visible angiogenesis-related phenotypes; however, these mice showed reproductive defects, with high rates of embryonic lethality in the second generation, at stages much earlier than the complete Ate1 knockout strain. While some of the early lethality originated from the subpopulation of embryos with homozygous Tek-Cre transgene--a problem that has not previously been reported for this commercial mouse strain--a distinct subpopulation of embryos had lethality at early post-implantation stages that could be explained only by a previously unknown defect in gametogenesis originating from Tek-driven Ate1 deletion in premeiotic germs cells. These results demonstrate a novel role of Ate1 in germ cell development.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Nicolae Adrian
authors.initials: NA
authors.lastname: Leu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurosaka
authors.forename: Anna
authors.initials: A
authors.lastname: Kashina
mesh_terms: D000199:Actins / Q000378:metabolism; D019881:Aminoacyltransferases / Q000235:genetics*; D000818:Animals; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D010064:Embryo Implantation; D005260:Female; D005718:Gametogenesis / Q000235:genetics*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D042787:Receptor, TIE-2
chemical_list: D000199:Actins; D019881:Aminoacyltransferases; C019727:arginyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse