title: Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control.
abstract: The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNA-damaging agents. We show here that Wip1 message is expressed in moderate levels in all organs, but is present at very high levels in the testes, particularly in the postmeiotic round spermatid compartment of the seminiferous tubules. We have confirmed that Wip1 mRNA is induced by ionizing radiation in mouse tissues in a p53-dependent manner. To further determine the normal biological function of Wip1 in mammalian organisms, we have generated Wip1-deficient mice. Wip1 null mice are viable but show a variety of postnatal abnormalities, including variable male runting, male reproductive organ atrophy, reduced male fertility, and reduced male longevity. Mice lacking Wip1 show increased susceptibility to pathogens and diminished T- and B-cell function. Fibroblasts derived from Wip1 null embryos have decreased proliferation rates and appear to be compromised in entering mitosis. The data are consistent with an important role for Wip1 in spermatogenesis, lymphoid cell function, and cell cycle regulation.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jene
authors.initials: J
authors.lastname: Choi
authors.forename: Bonnie
authors.initials: B
authors.lastname: Nannenga
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Demidov
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Bulavin
authors.forename: Austin
authors.initials: A
authors.lastname: Cooney
authors.forename: Cory
authors.initials: C
authors.lastname: Brayton
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Innocent N
authors.initials: IN
authors.lastname: Mbawuike
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001824:Body Constitution; D002453:Cell Cycle / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006801:Humans; D007107:Immune System / Q000502:physiology*; D017403:In Situ Hybridization; D007668:Kidney / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000502:physiology*; D000071636:Protein Phosphatase 2C; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D012098:Reproduction; D013091:Spermatogenesis; D013154:Spleen / Q000502:physiology / Q000528:radiation effects; D013234:Stem Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D013737:Testis / Q000502:physiology / Q000528:radiation effects
chemical_list: C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C