Submitted to: Molecular and Cellular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2001
Publication Date: 2/1/2002
Citation: Choi, J., Nannenga, B., Demidov, O.N., Bulavin, D.V., Cooney, A., Brayton, C., Zhang, Y., Mbawuike, I.N., Bradley, A., Appella, E., Donehower, L.A. 2002. Mice deficient for the wild-type p53-induced phosphatase gene (wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Molecular and Cellular Biology. 22(4):1094-105.
Interpretive Summary: This is a peer reviewed article describing the knock out of a gene in the mouse and analyzing its consequences. The gene is wip1, which is regulated by the cancer gene p53. Inactivation of this gene leads to defects in the immune system and the male reproductive system.
Technical Abstract: The Wip1 gene is a type 2C serine/threonine phosphatase that is induced in a p53-dependent manner by UV treatment of human cells. 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 post-meiotic round spermatid compartment of the seminiferous tubules. We have also confirmed that Wip1 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, reduced male longevity, and diminished T and B cell function. Fibroblasts derived from Wip1 null embryos are severely compromised in their division rate and appear to have reduced S phase entry and a less efficient G1 arrest in response to ionizing radiation. The data are consistent with a critical role for the Wip1 phosphatase in spermatogenesis, lymphoid cell function, and cell cycle regulation.