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Nature


Title:"p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours"
Author(s):Yang A; Walker N; Bronson R; Kaghad M; Oosterwegel M; Bonnin J; Vagner C; Bonnet H; Dikkes P; Sharpe A; McKeon F; Caput D;
Address:"Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA"
Journal Title:Nature
Year:2000
Volume:404
Issue:6773
Page Number:99 - 103
DOI: 10.1038/35003607
ISSN/ISBN:0028-0836 (Print) 0028-0836 (Linking)
Abstract:"p73 (ref. 1) has high homology with the tumour suppressor p53 (refs 2-4), as well as with p63, a gene implicated in the maintenance of epithelial stem cells. Despite the localization of the p73 gene to chromosome 1p36.3, a region of frequent aberration in a wide range of human cancers, and the ability of p73 to transactivate p53 target genes, it is unclear whether p73 functions as a tumour suppressor. Here we show that mice functionally deficient for all p73 isoforms exhibit profound defects, including hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways. In contrast to p53-deficient mice, however, those lacking p73 show no increased susceptibility to spontaneous tumorigenesis. We report the mechanistic basis of the hippocampal dysgenesis and the loss of pheromone responses, and show that new, potentially dominant-negative, p73 variants are the predominant expression products of this gene in developing and adult tissues. Our data suggest that there is a marked divergence in the physiological functions of the p53 family members, and reveal unique roles for p73 in neurogenesis, sensory pathways and homeostatic control"
Keywords:"Abnormalities, Multiple/genetics Animals DNA-Binding Proteins/deficiency/genetics/*physiology Embryonic and Fetal Development/*physiology Female Gene Targeting *Genes, Tumor Suppressor Hippocampus/abnormalities Hydrocephalus/genetics Inflammation/genetics;"
Notes:"MedlineYang, A Walker, N Bronson, R Kaghad, M Oosterwegel, M Bonnin, J Vagner, C Bonnet, H Dikkes, P Sharpe, A McKeon, F Caput, D eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 2000/03/15 Nature. 2000 Mar 2; 404(6773):99-103. doi: 10.1038/35003607"

 
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