Gene Expression Profiles Define a Key Checkpoint for Type 1 Diabetes in NOD Mice

Sarah E. Eckenrode, Qingguo Ruan, Ping Yang, Weipeng Zheng, Richard A McIndoe, Jin-Xiong She

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

cDNA microarrays with > 11,000 cDNA clones from an NOD spleen cDNA library were used to identify temporal gene expression changes in NOD mice (1-10 weeks), which spontaneously develop type 1 diabetes, and changes between NOD and NOD congenic mice (NO-D.Idd3/Idd10 and NOD.B10Sn-H2b), which have near zero incidence of insulitis and diabetes. The expression profiles identified two distinct groups of mice corresponding to an immature (1-4 weeks) and mature (6-10 weeks) state. The rapid switch of gene expression occurring, around 5 weeks of age defines a key immunological checkpoint. Sixty-two known genes are upregulated, and 18 are downregulated at this checkpoint in the NOD. The expression profiles are consistent with increased antibody production, antigen presentation, and cell proliferation associated with an active autoimmuneresponse. Seven of these genes map to confirmed diabetes susceptibility regions. Of these seven, three are excellent candidate genes not previously implicated in type 1 diabetes. Ten genes are differentially expressed between the NOD and congenic NOD at the immature stage (Hspa8, Hif1a, and several involved in cellular functions), while the other 70 genes exhibit expression differences during the mature (6-10 week) stage, suggesting that the expression differences of a small number of genes before onset of insulitis determine the disease progression.

Original languageEnglish (US)
Pages (from-to)366-375
Number of pages10
JournalDiabetes
Volume53
Issue number2
DOIs
StatePublished - Feb 1 2004

Fingerprint

Inbred NOD Mouse
Type 1 Diabetes Mellitus
Transcriptome
Genes
Gene Expression
Switch Genes
Congenic Mice
Antigen Presentation
Oligonucleotide Array Sequence Analysis
Gene Library
Antibody Formation
Disease Progression
Down-Regulation
Spleen
Complementary DNA
Clone Cells
Cell Proliferation
Incidence

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Gene Expression Profiles Define a Key Checkpoint for Type 1 Diabetes in NOD Mice. / Eckenrode, Sarah E.; Ruan, Qingguo; Yang, Ping; Zheng, Weipeng; McIndoe, Richard A; She, Jin-Xiong.

In: Diabetes, Vol. 53, No. 2, 01.02.2004, p. 366-375.

Research output: Contribution to journalArticle

Eckenrode, Sarah E. ; Ruan, Qingguo ; Yang, Ping ; Zheng, Weipeng ; McIndoe, Richard A ; She, Jin-Xiong. / Gene Expression Profiles Define a Key Checkpoint for Type 1 Diabetes in NOD Mice. In: Diabetes. 2004 ; Vol. 53, No. 2. pp. 366-375.
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