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Congenic mapping identifies a novel Idd9 subregion regulating type 1 diabetes in NOD mice
Ist Teil von
Immunogenetics (New York), 2017-03, Vol.69 (3), p.193-198
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
Type 1 diabetes (T1D) results from complex interactions between genetic and environmental factors. The nonobese diabetic (NOD) mouse develops spontaneous T1D and has been used extensively to study the genetic control of this disease. T1D is suppressed in NOD mice congenic for the C57BL/10 (B10)-derived
Idd9
resistance region on chromosome 4. Previous studies conducted by other investigators have identified four subregions (
Idd9.1
,
Idd9.2
,
Idd9.3
, and
Idd9.4
) where B10-derived genes suppress T1D development in NOD mice. We independently generated and characterized six congenic strains containing B10-derived intervals that partially overlap with the
Idd9.1
and
Idd9.4
regions. T1D incidence studies have revealed a new B10-derived resistance region proximal to
Idd9.1
. Our results also indicated that a B10-derived gene(s) within the
Idd9.4
region suppressed the diabetogenic activity of CD4 T cells and promoted CD103 expression on regulatory T cells indicative of an activated phenotype. In addition, we suggest the presence of a B10-derived susceptibility gene(s) in the
Idd9.1
/
Idd9.4
region. These results provide additional information to improve our understanding of the complex genetic control by the
Idd9
region.