Susceptibility to streptozotocin-induced diabetes is mapped to mouse chromosome 11.
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.
Babaya
Naru
N
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Ikegami
Hiroshi
H
Fujisawa
Tomomi
T
Nojima
Koji
K
Itoi-Babaya
Michiko
M
Inoue
Kaori
K
Ohno
Tamio
T
Shibata
Masao
M
Ogihara
Toshio
T
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D040641:Quantitative Trait Loci / Q000235:genetics; D013311:Streptozocin
D009687:Nuclear Proteins; D013311:Streptozocin; D010088:Oxidoreductases; C105231:nucleoredoxin