TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor

Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18952-7. doi: 10.1073/pnas.1221172110. Epub 2013 Nov 4.


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.

Keywords: CGRP; NGF; p53 family; sciatic nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Computational Biology
  • Mice
  • Mice, Knockout
  • Miniature Postsynaptic Potentials / genetics
  • Myelin Sheath / metabolism
  • Nervous System Malformations / genetics*
  • Nervous System Malformations / pathology
  • Neurites / metabolism
  • Neurites / pathology*
  • Nuclear Proteins / genetics*
  • Receptors, Nerve Growth Factor / deficiency*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation / genetics


  • Nuclear Proteins
  • Receptors, Nerve Growth Factor
  • TNFRSF16 protein, mouse
  • delta Np73, mouse