title: TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor.
abstract: Total and N-terminal isoform selective p73 knockout mice show a variety of central nervous system defects. Here we show that TAp73 is a transcriptional activator of p75 neurotrophin receptor (p75(NTR)) and that p75(NTR) mRNA and protein levels are strongly reduced in the central and peripheral nervous systems of p73 knockout mice. In parallel, primary cortical neurons from p73 knockout mice showed a reduction in neurite outgrowth and in nerve growth factor-mediated neuronal differentiation, together with reduced miniature excitatory postsynaptic current frequencies and behavioral defects. p73 null mice also have impairments in the peripheral nervous system with reduced thermal sensitivity, axon number, and myelin thickness. At least some of these morphological and functional impairments in p73 null cells can be rescued by p75(NTR) re-expression. Together, these data demonstrate that loss of p75(NTR) contributes to the neurological phenotype of p73 knockout mice.
authors.affiliation: Toxicology Unit, Medical Research Council, Leicester LE1 9HN, United Kingdom.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Niklison-Chirou
authors.forename: Joern R
authors.initials: JR
authors.lastname: Steinert
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.forename: Richard A
authors.initials: RA
authors.lastname: Knight
authors.forename: David
authors.initials: D
authors.lastname: Dinsdale
authors.forename: Antonio
authors.initials: A
authors.lastname: Cattaneo
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D019295:Computational Biology; D051379:Mice; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology; D016501:Neurites / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C454920:delta Np73, mouse
keywords: CGRP; NGF; p53 family; sciatic nerve