Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control.
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.
Choi
Jene
J
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nannenga
Bonnie
B
Demidov
Oleg N
ON
Bulavin
Dmitry V
DV
Cooney
Austin
A
Brayton
Cory
C
Zhang
Yongxin
Y
Mbawuike
Innocent N
IN
Bradley
Allan
A
Appella
Ettore
E
Donehower
Lawrence A
LA
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
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