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The iddm4 Locus Segregates With Diabetes Susceptibility in Congenic WF.iddm4 Rats

Identifieur interne : 001110 ( Main/Exploration ); précédent : 001109; suivant : 001111

The iddm4 Locus Segregates With Diabetes Susceptibility in Congenic WF.iddm4 Rats

Auteurs : John P. Mordes [États-Unis] ; Jean Leif [États-Unis] ; Stephen Novak ; Cheryl Descipio ; Dale L. Greiner [États-Unis] ; Elizabeth P. Blankenhorn

Source :

Diabetes [ 0012-1797 ] ; 2002.

RBID : PMC:4034451

Abstract

Viral antibody–free BBDR and WF rats never develop spontaneous diabetes. BBDR rats, however, develop autoimmune diabetes after perturbation of the immune system, e.g., by viral infection. We previously identified a disease-susceptibility locus in the BBDR rat, iddm4, which is associated with the development of autoimmune diabetes after treatment with polyinosinic:polycytidylic acid and an antibody that depletes ART2⁺ regulatory cells. We have now developed lines of congenic WF.iddm4 rats and report that in an intercross of N5 generation WF.iddm4 rats, ∼70% of animals either homozygous or heterozygous for the BBDR origin allele of iddm4 became hyperglycemic after treatment to induce diabetes. Fewer than 20% of rats expressing the WF origin allele of iddm4 became diabetic. Testing the progeny of various recombinant N5 WF.iddm4 congenic rats for susceptibility to diabetes suggests that iddm4 is centered on a small segment of chromosome 4 bounded by the proximal marker D4Rat135 and the distal marker D4Got51, an interval of <2.8 cM. The allele at iddm4 has 79% sensitivity and 80% specificity in prediction of diabetes in rats that are segregating for this locus. These characteristics suggest that iddm4 is one of the most powerful non–major histocompatibility complex determinants of susceptibility to autoimmune diabetes described to date.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034451

PubMed: 12401717
PubMed Central: 4034451

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The <italic>iddm4</italic>
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<front><div type="abstract" xml:lang="en"><p id="P1">Viral antibody–free BBDR and WF rats never develop spontaneous diabetes. BBDR rats, however, develop autoimmune diabetes after perturbation of the immune system, e.g., by viral infection. We previously identified a disease-susceptibility locus in the BBDR rat, <italic>iddm4</italic>
, which is associated with the development of autoimmune diabetes after treatment with polyinosinic:polycytidylic acid and an antibody that depletes ART2<sup>+</sup>
 regulatory cells. We have now developed lines of congenic WF.<italic>iddm4</italic>
 rats and report that in an intercross of N5 generation WF.<italic>iddm4</italic>
 rats, ∼70% of animals either homozygous or heterozygous for the BBDR origin allele of <italic>iddm4</italic>
 became hyperglycemic after treatment to induce diabetes. Fewer than 20% of rats expressing the WF origin allele of <italic>iddm4</italic>
 became diabetic. Testing the progeny of various recombinant N5 WF.<italic>iddm4</italic>
 congenic rats for susceptibility to diabetes suggests that <italic>iddm4</italic>
 is centered on a small segment of chromosome 4 bounded by the proximal marker <italic>D4Rat135</italic>
 and the distal marker <italic>D4Got51</italic>
, an interval of <2.8 cM. The allele at <italic>iddm4</italic>
 has 79% sensitivity and 80% specificity in prediction of diabetes in rats that are segregating for this locus. These characteristics suggest that <italic>iddm4</italic>
 is one of the most powerful non–major histocompatibility complex determinants of susceptibility to autoimmune diabetes described to date.</p>
</div>
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The iddm4 Locus Segregates With Diabetes Susceptibility in Congenic WF.iddm4 Rats

The iddm4 Locus Segregates With Diabetes Susceptibility in Congenic WF.iddm4 Rats

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Abstract

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