A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2.

Diabetologia
N BabayaG S Eisenbarth

Abstract

We describe a novel model of insulin-deficient diabetes with a single copy of the gene encoding insulin 1 (Ins1) and no gene encoding insulin 2 (Ins2). We constructed five lines of mice: mice with two copies of Ins1 (NOD( Ins1+/+,Ins2-/-)), mice with a single copy of Ins1 (NOD( Ins1+/-,Ins2-/-)), mice with two copies of Ins2 (NOD( Ins1-/-,Ins2+/+)), mice with a single copy of Ins2 (NOD( Ins1-/-,Ins2+/-)) and NOD( Ins1+/-,Ins2-/-) mice with a transgene encoding B16:Ala proinsulin. By 10 weeks of age, all male NOD( Ins1+/-,Ins2-/-) mice were diabetic, whereas all female NOD( Ins1+/-,Ins2-/-) were not diabetic (p < 0.0001). In contrast, neither male nor female NOD( Ins1-/-,Ins2+/-) with a single copy of Ins2 (rather than single copy of Ins1) developed early diabetes and no mice with two copies of either gene developed early diabetes. Islets of the diabetic male NOD( Ins1+/-,Ins2-/-) at this early age had no lymphocyte infiltration. Instead there was heterogeneous (between islet cells) weak staining for insulin. Although only male NOD( Ins1+/-,Ins2-/-) mice developed diabetes, both male and female NOD( Ins1+/-,Ins2-/-) mice had markedly decreased insulin content. In NOD( Ins1+/+,Ins2-/-), there was also a significant decrease in in...Continue Reading

References

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Citations

Feb 5, 2008·Genetics·Meng-Shin ShiaoHon-Tsen Yu
Jan 1, 2012·The Review of Diabetic Studies : RDS·John P DriverClayton E Mathews
Feb 7, 2014·Annual Review of Immunology·Emil R Unanue
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Jul 25, 2007·Molecular Biology and Evolution·Meng-Shin ShiaoManyuan Long
Apr 18, 2018·Journal of Cellular Biochemistry·Sang Ah YiJeung-Whan Han
Mar 5, 2014·Current Protocols in Mouse Biology·Edward H Leiter, Andrew Schile
Nov 3, 2009·The Journal of Biological Chemistry·Israel HodishPeter Arvan
Mar 28, 2013·American Journal of Physiology. Endocrinology and Metabolism·Martín CrivelloVictoria Lux-Lantos
Dec 10, 2019·Biochemical and Biophysical Research Communications·Shraddha ChakrabortyDwaipayan Bharadwaj

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