Identification of Four Mouse Diabetes Candidate Genes Altering β-Cell Proliferation

被引：38

作者：

Kluth, Oliver ^{[1
,2
]}

Matzke, Daniela ^{[1
,2
]}

Kamitz, Anne ^{[1
,2
]}

Jaehnert, Markus ^{[1
,2
]}

Vogel, Heike ^{[1
,2
]}

Scherneck, Stephan ^{[1
,2
,3
]}

Schulze, Matthias ^{[2
,4
]}

Staiger, Harald ^{[2
,5
,6
]}

Machicao, Fausto ^{[2
,6
]}

Haering, Hans-Ulrich ^{[2
,5
,6
]}

Joost, Hans-Georg ^{[2
,7
]}

Schuermann, Annette ^{[1
,2
]}

机构：

[1] German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Nuthetal, Germany

[2] German Ctr Diabet Res DZD, Neuherberg, Germany

[3] Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmacol & Toxicol, Braunschweig, Germany

[4] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany

[5] Univ Hosp Tubingen, Dept Internal Med, Tubingen, Germany

[6] Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany

[7] German Inst Human Nutr Potsdam Rehbrucke, Dept Pharmacol, Nuthetal, Germany

来源：

PLOS GENETICS | 2015年 / 11卷 / 09期

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; SUSCEPTIBILITY GENES; OBESITY; GROWTH; MICE; TBC1D1; PREVENTS; PATHWAY; BINDING; STRAIN;

D O I：

10.1371/journal.pgen.1005506

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Beta-cell apoptosis and failure to induce beta-cell regeneration are hallmarks of type 2-like diabetes in mouse models. Here we show that islets from obese, diabetes-susceptible New Zealand Obese (NZO) mice, in contrast to diabetes-resistant C57BL/6J (B6)-ob/ob mice, do not proliferate in response to an in-vivo glucose challenge but lose their beta-cells. Genome-wide RNAseq based transcriptomics indicated an induction of 22 cell cycle-associated genes in B6-ob/ob islets that did not respond in NZO islets. Of all genes differentially expressed in islets of the two strains, seven mapped to the diabesity QTL Nob3, and were hypomorphic in either NZO (Lefty1, Apoa2, Pcp4l1, Mndal, Slamf7, Pydc3) or B6 (Ifi202b). Adenoviral overexpression of Lefty1, Apoa2, and Pcp4l1 in primary islet cells increased proliferation, whereas overexpression of Ifi202b suppressed it. We conclude that the identified genes in synergy with obesity and insulin resistance participate in adaptive islet hyperplasia and prevention from severe diabetes in B6-ob/ob mice.

引用

页数：18

共 36 条

[1] Differential expression analysis for sequence count data [J].