Identification of Novel Genes Involved in Hyperglycemia in Mice

被引:4
作者
Jonas, Wenke [1 ,2 ]
Kluth, Oliver [1 ,2 ]
Helms, Anett [1 ,2 ]
Voss, Sarah [1 ,2 ]
Jahnert, Markus [1 ,2 ]
Gottmann, Pascal [1 ,2 ]
Speckmann, Thilo [1 ,2 ]
Knebel, Birgit [2 ,3 ]
Chadt, Alexandra [2 ,3 ]
Al-Hasani, Hadi [2 ,3 ]
Schuermann, Annette [1 ,2 ,4 ]
Vogel, Heike [1 ,2 ,5 ,6 ]
机构
[1] German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Expt Diabetol, D-14558 Nuthetal, Germany
[2] German Ctr Diabet Res DZD, D-85764 Munich, Germany
[3] Heinrich Heine Univ, Med Fac, German Diabet Ctr DDZ, Inst Clin Biochem & Pathobiochem, D-40225 Dusseldorf, Germany
[4] Univ Potsdam, Inst Nutr Sci, D-14558 Nuthetal, Germany
[5] German Inst Human Nutr Potsdam Rehbruecke DIfE, Res Grp Genet Obes, D-14558 Nuthetal, Germany
[6] Univ Potsdam, Fac Hlth Sci Brandenburg, Res Grp Mol & Clin Life Sci Metab Dis, D-14469 Potsdam, Germany
关键词
beta-cell; diabetes; proliferation; apoptosis; QTL; S100; PROTEINS; MOUSE; EXPRESSION; ISLETS; QTL;
D O I
10.3390/ijms23063205
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.
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页数:13
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