RGD Reference Report - Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss. - Rat Genome Database

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Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss.

Authors: Chen, S  Rio, C  Ji, RR  Dikkes, P  Coggeshall, RE  Woolf, CJ  Corfas, G 
Citation: Chen S, etal., Nat Neurosci 2003 Nov;6(11):1186-93. Epub 2003 Oct 12.
RGD ID: 734941
Pubmed: PMID:14555954   (View Abstract at PubMed)
DOI: DOI:10.1038/nn1139   (Journal Full-text)

Here we studied the role of signaling through ErbB-family receptors in interactions between unmyelinated axons and non-myelinating Schwann cells in adult nerves. We generated transgenic mice that postnatally express a dominant-negative ErbB receptor in non-myelinating but not in myelinating Schwann cells. These mutant mice present a progressive peripheral neuropathy characterized by extensive Schwann cell proliferation and death, loss of unmyelinated axons and marked heat and cold pain insensitivity. At later stages, C-fiber sensory neurons die by apoptosis, a process that may result from reduced GDNF (glial cell line-derived neurotrophic factor) expression in the sciatic nerve. Neuregulin 1 (NRG1)-ErbB signaling mediates, therefore, reciprocal interactions between non-myelinating Schwann cells and unmyelinated sensory neuron axons that are critical for Schwann cell and C-fiber sensory neuron survival. This study provides new insights into ErbB signaling in adult Schwann cells, the contribution of non-myelinating Schwann cells in maintaining trophic support of sensory neurons, and the possible role of disrupted ErbB signaling in peripheral sensory neuropathies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
peripheral nervous system disease  ISOErbb4 (Mus musculus)734941; 734941 RGD 
peripheral nervous system disease  IMP 734941 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Mus musculus)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Homo sapiens)
ERBB4  (erb-b2 receptor tyrosine kinase 4)


Additional Information