Document Detail

Mutation in neurofilament transgene implicates RNA processing in the pathogenesis of neurodegenerative disease.
MedLine Citation:
PMID:  9952405     Owner:  NLM     Status:  MEDLINE    
A mouse neurofilament light subunit (NF-L) transgene with a 36 bp c-myc insert at the end of the coding region was found to have neuropathic effects on enteric and motor neurons of transgenic mice. The severity of phenotype was related directly to the levels of transgenic mRNA expression. High levels of transgene expression were lethal to newborn pups, causing profound alterations in the development of the enteric nervous system and extensive vacuolar changes in motor neurons. Lower levels of transgene expression led to a transient stunting of growth and focal alterations of enteric and motor neurons. Because the positioning of the c-myc insert coincided with the location of the major stability determinant of the NF-L mRNA (Cañete-Soler et al., 1998a,b), additional studies were undertaken. These studies showed that the c-myc insert alters the ribonucleoprotein (RNP) complexes that bind to the stability determinant and disrupts their ability to regulate the stability of the transcripts. The findings indicate that expression of an NF-L transgene with a mutant mRNA stability determinant is highly disruptive to enteric and motor neurons and implicate alterations in RNA processing in the pathogenesis of a neurodegenerative condition.
R Cañete-Soler; D G Silberg; M D Gershon; W W Schlaepfer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  19     ISSN:  0270-6474     ISO Abbreviation:  J. Neurosci.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-02-25     Completed Date:  1999-02-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1273-83     Citation Subset:  IM    
Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104-6079, USA.
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MeSH Terms
3' Untranslated Regions / genetics
CCAAT-Enhancer-Binding Proteins*
DNA Transposable Elements
DNA-Binding Proteins / genetics*
Enteric Nervous System / cytology,  physiology
Genes, myc / genetics
Growth / genetics,  physiology
Intestine, Small / growth & development,  innervation
Mice, Transgenic
Motor Neurons / physiology,  ultrastructure
Mutation / physiology*
NFI Transcription Factors
Neurodegenerative Diseases / genetics*,  physiopathology*
Neurofilament Proteins / genetics*
Nuclear Proteins
RNA Processing, Post-Transcriptional / physiology*
RNA, Messenger / biosynthesis,  genetics
Ribonucleoproteins / biosynthesis
Transcription Factors / genetics*
Transgenes / genetics*
Y-Box-Binding Protein 1
Grant Support
Reg. No./Substance:
0/3' Untranslated Regions; 0/CCAAT-Enhancer-Binding Proteins; 0/DNA Transposable Elements; 0/DNA-Binding Proteins; 0/NFI Transcription Factors; 0/Neurofilament Proteins; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Ribonucleoproteins; 0/Transcription Factors; 0/Y-Box-Binding Protein 1; 0/YBX1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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