Document Detail


Identification of a novel nonsense mutation on the Pax3 gene in ENU-derived white belly spotting mice and its genetic interaction with c-Kit.
MedLine Citation:
PMID:  20095975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the course of a large-scale screening program of N-ethyl-N-nitrosourea mutagenesis, we isolated two semidominant mutation lines with white belly spotting, named as wps and wbs. Direct sequencing detected a nucleotide G-to-A transversion in exon 2 of the c-Kit gene in wps, which resulted in a missense D60N mutation. Another mutant, wbs, was mapped to chromosome 1 by genome-wide linkage analysis. In 93 meioses, the wbs locus was confined to a 5.2-Mb region between D1Mit380 and D1Mit215, including the Pax3 gene. A nonsense mutation K107X on the Pax3 coding region in wbs mice was identified, causing the loss of Pax3 protein in the homozygous mutant. We further demonstrated that Pax3 exhibited genetic interaction with c-Kit by intercrossing the wps and wbs mice. Further, Pax3 transactivated the c-Kit promoter in different cell lines. However, electrophoretic mobility shift assays showed that Pax3 did not bind to the c-Kit promoter, indicating that Pax3 may interact with c-Kit in an indirect way. This expands our understanding of the intricate regulatory network governing the melanocyte development.
Authors:
Xiao-Li Guo; Hai-Bin Ruan; Yan Li; Xiang Gao; Wei Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-22
Journal Detail:
Title:  Pigment cell & melanoma research     Volume:  23     ISSN:  1755-148X     ISO Abbreviation:  Pigment Cell Melanoma Res     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-16     Completed Date:  2010-08-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101318927     Medline TA:  Pigment Cell Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  252-62     Citation Subset:  IM    
Affiliation:
Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Animals
COS Cells
Cells, Cultured
Cercopithecus aethiops
Codon, Nonsense*
Ethylnitrosourea
Female
Humans
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred CBA
Mutagenesis / genetics
Paired Box Transcription Factors / genetics*,  metabolism
Phenotype
Proto-Oncogene Proteins c-kit / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Codon, Nonsense; 0/Paired Box Transcription Factors; 138016-91-8/Pax3 protein, mouse; 759-73-9/Ethylnitrosourea; EC 2.7.10.1/Proto-Oncogene Proteins c-kit

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


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