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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2001-10-19
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pubmed:abstractText |
Here we report an analysis of two candidate genes for the t(w73) implantation mutation. The t(w73) gene maps to a 20-cM region of mouse Chromosome (Chr) 17 known as the t-complex, which exists in a wild-type and t haplotype form in present-day mice. The t haplotype variants contain several mutant alleles affecting male fertility and embryonic viability and offer the opportunity to identify genes critical for these processes. t(w73) homozygous embryos are defective in trophoblast production and fail to implant adequately, with death occurring at approximately 7.5 days post coitum (pc). Two recently described organic cation transporter genes, Slc22a2 (Orct2) and Slc22a3 (Orct3), fulfill criteria predicted for t(w73) candidate genes, since both map to the previously defined 500-kb t(w73) minimal region and both are also expressed in 7.5 days pc post-implantation embryos. The genomic locus of the Orct2 gene appears similar in wild-type and t(w73) chromosomes. In contrast, the genomic locus of Orct3 is amplified and displays an altered expression profile in all t haplotype variant chromosomes tested. In addition, Orct3 shows a t(w73) specific polymorphism. To test whether either Orct2 or Orct3 is involved in the t(w73) phenotype, we have performed a genetic rescue experiment using YAC transgenes overexpressing Orct2, and genetic complementation with an allele in which the Orct3 gene was inactivated by homologous recombination. The results eliminate both Orct2 and Orct3 as candidates and further reduce the critical region containing the t(w73) mutant from 500 kb to 200 kb.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0938-8990
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
734-40
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11641723-Animals,
pubmed-meshheading:11641723-Blotting, Northern,
pubmed-meshheading:11641723-Blotting, Southern,
pubmed-meshheading:11641723-Carrier Proteins,
pubmed-meshheading:11641723-Chromosomes, Artificial, Yeast,
pubmed-meshheading:11641723-Crosses, Genetic,
pubmed-meshheading:11641723-DNA Primers,
pubmed-meshheading:11641723-Embryonic Development,
pubmed-meshheading:11641723-Female,
pubmed-meshheading:11641723-Genetic Complementation Test,
pubmed-meshheading:11641723-Haplotypes,
pubmed-meshheading:11641723-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11641723-Mice,
pubmed-meshheading:11641723-Mice, Transgenic,
pubmed-meshheading:11641723-Microtubule-Associated Proteins,
pubmed-meshheading:11641723-Mutation,
pubmed-meshheading:11641723-Nuclear Proteins,
pubmed-meshheading:11641723-Organic Cation Transport Proteins,
pubmed-meshheading:11641723-Organic Cation Transporter 1,
pubmed-meshheading:11641723-Polymorphism, Genetic,
pubmed-meshheading:11641723-Pregnancy,
pubmed-meshheading:11641723-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11641723-Sequence Analysis, DNA,
pubmed-meshheading:11641723-t-Complex Genome Region
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pubmed:year |
2001
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pubmed:articleTitle |
Genetic analysis of the organic cation transporter genes Orct2/Slc22a2 and Orct3/Slc22a3 reduces the critical region for the t haplotype mutant t(w73) to 200 kb.
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pubmed:affiliation |
Netherlands Cancer Institute, Dept. of Molecular Genetics (H5), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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