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

Abstract

To study the contribution of beta-cell vulnerability to susceptibility to diabetes, we studied beta-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 beta cells is determined by a gene or genes on Chr 11, which may also contribute to susceptibility to spontaneous diabetes.

• Authors: Naru Babaya, Hiroshi Ikegami, Tomomi Fujisawa, Koji Nojima, Michiko Itoi-Babaya, Kaori Inoue, Tamio Ohno, Masao Shibata, Toshio Ogihara
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 328 Issue 1 Pg. 158-64 (Mar 04 2005) ISSN: 0006-291X [Print] United States
• PMID: 15670764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nuclear Proteins
• Streptozocin
• Oxidoreductases
• nucleoredoxin

Topics

• Animals
• Base Sequence
• Chromosome Mapping (methods)
• Diabetes Mellitus, Experimental (genetics, metabolism)
• Gene Expression Regulation (genetics)
• Genetic Predisposition to Disease (genetics)
• Mice
• Molecular Sequence Data
• Nuclear Proteins (genetics, metabolism)
• Oxidoreductases (genetics, metabolism)
• Quantitative Trait Loci (genetics)
• Streptozocin