p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours

ANNIE YANG*, NANCY WALKER†, RODERICK BRONSON‡, MOURAD KAGHAD†, MARIETTE OOSTERWEGEL§, JACQUES BONNIN†, CHRISTINE VAGNER†, HELENE BONNET†, PIETER DIKKES, ARLENE SHARPE§, FRANK MCKEON* & DANIEL CAPUT†

Nature 404, 99-103 (2000)


Abstract

p73 has high homology with the tumour suppressor p53. Although 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 they 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. They 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. Their 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.

Reference

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