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p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours
p73 (ref. 1) has high homology with the tumour suppressor p53 (refs 2,3,4), 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 abi...
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Published in: | Nature (London) 2000-03, Vol.404 (6773), p.99-103 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | p73 (ref. 1) has high homology with the tumour
suppressor p53 (refs 2,3,4), 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. |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/35003607 |