title: Tankyrase 1 and tankyrase 2 are essential but redundant for mouse embryonic development.
abstract: Tankyrases are proteins with poly(ADP-ribose) polymerase activity. Human tankyrases post-translationally modify multiple proteins involved in processes including maintenance of telomere length, sister telomere association, and trafficking of glut4-containing vesicles. To date, however, little is known about in vivo functions for tankyrases. We recently reported that body size was significantly reduced in mice deficient for tankyrase 2, but that these mice otherwise appeared developmentally normal. In the present study, we report generation of tankyrase 1-deficient and tankyrase 1 and 2 double-deficient mice, and use of these mutant strains to systematically assess candidate functions of tankyrase 1 and tankyrase 2 in vivo. No defects were observed in development, telomere length maintenance, or cell cycle regulation in tankyrase 1 or tankyrase 2 knockout mice. In contrast to viability and normal development of mice singly deficient in either tankyrase, deficiency in both tankyrase 1 and tankyrase 2 results in embryonic lethality by day 10, indicating that there is substantial redundancy between tankyrase 1 and tankyrase 2, but that tankyrase function is essential for embryonic development.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. chiangj@mail.nih.gov
authors.forename: Y Jeffrey
authors.initials: YJ
authors.lastname: Chiang
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hsiao
authors.forename: Dena
authors.initials: D
authors.lastname: Yver
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Cushman
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Susan
authors.initials: S
authors.lastname: Smith
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hodes
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D038501:Tankyrases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D007328:Insulin; D038501:Tankyrases; C498822:Tnks protein, mouse; C511054:tankyrase-2, mouse; D005947:Glucose