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

Maria Victoria Niklison-Chirou, Joern R. Steinert, Massimiliano Agostini, Richard A. Knight, David Dinsdale, Antonio Cattaneo, Tak W. Mak, Gerry Melino

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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 (p75NTR) and that p75NTR 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 p75NTR re-expression. Together, these data demonstrate that loss of p75NTR contributes to the neurological phenotype of p73 knockout mice.

Original languageEnglish
Pages (from-to)18952-18957
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
Publication statusPublished - 19 Nov 2013

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