Source:http://linkedlifedata.com/resource/pubmed/id/15587270
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rdf:type | |
lifeskim:mentions |
umls-concept:C0006104,
umls-concept:C0012546,
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0076851,
umls-concept:C0185117,
umls-concept:C0337112,
umls-concept:C0475264,
umls-concept:C1280500,
umls-concept:C1517676,
umls-concept:C1524075,
umls-concept:C1527148,
umls-concept:C1708726,
umls-concept:C2911684
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pubmed:issue |
5
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pubmed:dateCreated |
2004-12-10
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pubmed:abstractText |
We report here knock-in of diphteria toxin A chain (dta) gene at the Ins2 locus, using the strategy previously employed to insert lacZ under control of the Ins2 promoter. Mutant Ins2(dta/+), Ins2(dta/lacZ) or Ins2(lacZ/+) mouse pups were generated by breeding and analyzed to study the effects of toxigenetic beta-cell ablation on islet development and to localize the extrapancreatic Ins2 expression site in the brain. Ins2(dta/+) and Ins2(dta/lacZ) pups developed a severe diabetic ketoacidosis and died rapidly. Histological analysis of their pancreas revealed that beta-cells completely disappeared in their islets as evidenced by loss of lacZ activity or insulin immunonostaining. beta-cell ablation did not alter the size of other islet cell populations which were normal at birth, although the glucagon-cell population was reduced by 85% at embryonic day E12.5. In the brain, comparative analysis of lacZ expression in Ins2(lacZ/+) and Ins2(dta/laZ) mice identified the choroid plexus (CP) as a major Ins2 expression site. This finding was confirmed by RT-PCR analysis of insulin transcripts in RNAs prepared from microdissected wild-type CP. Transcripts for other key beta-cell markers, with the notable exception of Pdx-1, were also found in CP RNAs. These results must revive interest in studies focused on extrapancreatic insulin gene expression.
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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 |
Oct
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pubmed:issn |
0962-8819
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
463-73
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15587270-Animals,
pubmed-meshheading:15587270-Choroid Plexus,
pubmed-meshheading:15587270-Diabetic Ketoacidosis,
pubmed-meshheading:15587270-Diphtheria Toxin,
pubmed-meshheading:15587270-Gene Expression Regulation, Developmental,
pubmed-meshheading:15587270-Genetic Vectors,
pubmed-meshheading:15587270-Insulin,
pubmed-meshheading:15587270-Islets of Langerhans,
pubmed-meshheading:15587270-Lac Operon,
pubmed-meshheading:15587270-Mice,
pubmed-meshheading:15587270-Mice, Transgenic,
pubmed-meshheading:15587270-Pancreas,
pubmed-meshheading:15587270-Peptide Fragments,
pubmed-meshheading:15587270-Promoter Regions, Genetic
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pubmed:year |
2004
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pubmed:articleTitle |
Knock-in of diphteria toxin A chain gene at Ins2 locus: effects on islet development and localization of Ins2 expression in the brain.
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pubmed:affiliation |
Institut Cochin, INSERM U567, CNRS UMR 8104, Université René Descartes, Département Génétique, Développement et Pathologie Moléculaire, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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