Source:http://linkedlifedata.com/resource/pubmed/id/16518687
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2006-3-6
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| pubmed:abstractText |
The murine beige mutant phenotype and the human Chediak-Higashi syndrome are caused by mutations in the murine Lyst (lysosomal trafficking regulator) gene and the human CHS gene, respectively. In this report we have analyzed a novel murine mutant Lyst allele, called Lyst(bg-grey), that had been found in an ENU mutation screen and named grey because of the grey coat color of affected mice. The phenotype caused by the Lyst(bg-grey) mutation was inherited in a recessive fashion. Melanosomes of melanocytes associated with hair follicles and the choroid layer of the eye, as well as melanosomes in the neural tube-derived pigment epithelium of the retina, were larger and irregularly shaped in homozygous mutants compared with those of wild-type controls. Secretory vesicles in dermal mast cells of the mutant skin were enlarged as well. Test crosses with beige homozygous mutant mice (Lyst(bg)) showed that double heterozygotes (Lyst(bg)/Lyst(bg-grey)) were phenotypically indistinguishable from either homozygous parent, demonstrating that the ENU mutation was an allele of the murine Lyst gene. RT-PCR analyses revealed the skipping of exon 25 in Lyst(bg-grey) mutants, which is predicted to cause a missense D2399E mutation and the loss of the following 77 amino acids encoded by exon 25 but leave the C-terminal end of the protein intact. Analysis of the genomic Lyst locus around exon 25 showed that the splice donor at the end of exon 25 showed a T-to-C transition point mutation. Western blot analysis suggests that the Lyst(bg-grey) mutation causes instability of the LYST protein. Because the phenotype of Lyst(bg) and Lyst(bg-grey) mutants is indistinguishable, at least with respect to melanosomes and secretory granules in mast cells, the Lyst(bg-grey) mutation defines a critical region for the stability of the murine LYST protein.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0938-8990
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
203-10
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| pubmed:meshHeading |
pubmed-meshheading:16518687-Amino Acid Sequence,
pubmed-meshheading:16518687-Animals,
pubmed-meshheading:16518687-Blotting, Western,
pubmed-meshheading:16518687-Exons,
pubmed-meshheading:16518687-Female,
pubmed-meshheading:16518687-Hair Color,
pubmed-meshheading:16518687-Heterozygote,
pubmed-meshheading:16518687-Homozygote,
pubmed-meshheading:16518687-Male,
pubmed-meshheading:16518687-Mast Cells,
pubmed-meshheading:16518687-Melanocytes,
pubmed-meshheading:16518687-Mice,
pubmed-meshheading:16518687-Mice, Inbred C57BL,
pubmed-meshheading:16518687-Mice, Knockout,
pubmed-meshheading:16518687-Molecular Sequence Data,
pubmed-meshheading:16518687-Mutation,
pubmed-meshheading:16518687-Pedigree,
pubmed-meshheading:16518687-Phenotype,
pubmed-meshheading:16518687-Pigment Epithelium of Eye,
pubmed-meshheading:16518687-Proteins,
pubmed-meshheading:16518687-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16518687-Secretory Vesicles,
pubmed-meshheading:16518687-Sequence Homology, Amino Acid
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| pubmed:year |
2006
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| pubmed:articleTitle |
Grey, a novel mutation in the murine Lyst gene, causes the beige phenotype by skipping of exon 25.
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| pubmed:affiliation |
Anatomisches Institut, Universität Bonn, Germany. f.runkel@uni-bonn.de
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| pubmed:publicationType |
Journal Article
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