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Susceptibility to streptozotocin-induced diabetes is mapped to mouse chromosome 11

Biochemical and Biophysical Research Communications, ISSN: 0006-291X, Vol: 328, Issue: 1, Page: 158-164
2005
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To study the contribution of β-cell vulnerability to susceptibility to diabetes, we studied β-cell vulnerability to a single high dose of streptozotocin (STZ) in an animal model of type 2 diabetes, the NSY mouse, a sister strain of the STZ-sensitive NOD mouse, in comparison with the STZ-resistant C3H mouse. NSY mice were found to be extremely sensitive to STZ. Introgression of a single Chr 11, where STZ-sensitivity was mapped in the NOD mouse, from NSY mice converted STZ-resistant C3H mice to STZ-sensitive. Two nucleotide substitutions were identified in the nucleoredoxin gene, a positional and functional candidate gene for STZ-induced diabetes on Chr 11. These data, together with the co-localization of type 1 ( Idd4 ) and type 2 ( Nidd1n ) susceptibility genes on Chr 11, suggest that the intrinsic vulnerability of pancreatic β cells is determined by a gene or genes on Chr 11, which may also contribute to susceptibility to spontaneous diabetes.

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