Abstract:
:It has been reported that an insulin 2 gene knockout, when bred onto nonobese diabetic (NOD) mice, accelerates diabetes. We produced insulin 1 gene knockout congenic NOD mice. In contrast to insulin 2, diabetes and insulitis were markedly reduced in insulin 1 knockout mice, with decreased and delayed diabetes in heterozygous females and no insulitis and diabetes in most homozygous female mice. Lack of insulitis was found for insulin 1 female homozygous knockout mice at 8, 12, and 37 weeks of age. Despite a lack of insulitis, insulin 1 homozygous knockout mice spontaneously expressed insulin autoantibodies. Administration of insulin peptide B:9-23 of both insulin 1 and 2 to NOD mice induced insulin autoantibodies. Insulin 1 is not the only lymphocytic target of NOD mice. Insulin 1 homozygous knockout islets, when transplanted into recently diabetic wild-type NOD mice, became infiltrated with lymphocytes and only transiently reversed diabetes. These observations indicate that loss of either insulin gene can influence progression to diabetes of NOD mice and suggest that the preproinsulin 1 gene is crucial for the spontaneous development of NOD insulitis and diabetes.
journal_name
Proc Natl Acad Sci U S Aauthors
Moriyama H,Abiru N,Paronen J,Sikora K,Liu E,Miao D,Devendra D,Beilke J,Gianani R,Gill RG,Eisenbarth GSdoi
10.1073/pnas.1834450100keywords:
subject
Has Abstractpub_date
2003-09-02 00:00:00pages
10376-81issue
18eissn
0027-8424issn
1091-6490pii
1834450100journal_volume
100pub_type
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