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 () and Daniel Caput ()
Additional contact information
Annie Yang: Harvard Medical School
Nancy Walker: Sanofi Recherche, Innopole B.P. 137
Roderick Bronson: Human Nutrition Research Center on Aging, Tufts University of School of Veterinary Medicine
Mourad Kaghad: Sanofi Recherche, Innopole B.P. 137
Mariette Oosterwegel: Brigham and Women's Hospital and Harvard Medical School
Jacques Bonnin: Sanofi Recherche, Innopole B.P. 137
Christine Vagner: Sanofi Recherche, Innopole B.P. 137
Helene Bonnet: Sanofi Recherche, Innopole B.P. 137
Pieter Dikkes: Children's Hospital
Arlene Sharpe: Brigham and Women's Hospital and Harvard Medical School
Frank McKeon: Harvard Medical School
Daniel Caput: Sanofi Recherche, Innopole B.P. 137

Nature, 2000, vol. 404, issue 6773, 99-103

Abstract: Abstract 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 cells5,6,7. Despite the localization of the p73 gene to chromosome 1p36.3, a region of frequent aberration in a wide range of human cancers1, and the ability of p73 to transactivate p53 target genes1, 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.

Date: 2000
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DOI: 10.1038/35003607

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