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.

Niklison Chirou, M., Steinert, J., Agostini, M., Knight, R., Dinsdale, D., Cattaneo, A., et al. (2013). TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(47), 18952-18957 [10.1073/pnas.1221172110].

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

AGOSTINI, MASSIMILIANO;MELINO, GENNARO
2013-11-19

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
Settore BIO/11
English
Animals; Nervous System Malformations; Miniature Postsynaptic Potentials; Brain; Mice; Myelin Sheath; Computational Biology; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation; Neurites; CGRP; Mice, Knockout; p53 family; Blotting, Western; sciatic nerve; Nuclear Proteins; Receptors, Nerve Growth Factor; NGF
Niklison Chirou, M., Steinert, J., Agostini, M., Knight, R., Dinsdale, D., Cattaneo, A., et al. (2013). TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(47), 18952-18957 [10.1073/pnas.1221172110].
Niklison Chirou, M; Steinert, J; Agostini, M; Knight, R; Dinsdale, D; Cattaneo, A; Mak, T; Melino, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/102756
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