Type 1 diabetes may be the outcome of good genes behaving badly

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Type 1 diabetes may be the outcome of good genes behaving badly

September 20th, 2008

http://www.thaindian.com/newsportal/entertainment/type-1-diabetes-may-be-the-out\

come-of-good-genes-behaving-badly_10097739.html

Washington, Sept 20 (ANI): Researchers from Stanford University have

revealed that type 1 diabetes may not be due to bad genes but rather to

good genes behaving badly.

Previous studies in identical twins have revealed that often one twin

develops type 1 diabetes while the other twin remains disease-free, this

may be due to how genetically at-risk individuals respond differently to

environmental stimuli.

In some cases, the immune system will respond in a benign fashion, while

in other cases it will begin an inflammatory response that can

ultimately lead to diabetes.

During the study, the research team led by C. Garrison Fathman, M.D.,

studied differences in gene expression between two groups of mice.

The first group, non-obese diabetic mice, spontaneously develop type 1

diabetes.

The second group, mice genetically identical to the first group except

for their MHC genes, responsible for causing diabetes.

The researchers looked at gene expression in three different tissues in

the diabetic and non-diabetic mice at separate times after birth.

In the first few weeks of life, they found an explosion of changes in

gene expression in the pancreatic lymph nodes, spleen and circulating

blood cells of the diabetic mice compared with those in the non-diabetic

mice.

At 8 weeks, this activity had quieted down. But several weeks later,

when the mice were 12 weeks old, a second explosion of changes in gene

expression occurred in the diabetic mice in all three tissues examined:

pancreatic lymph nodes, spleen and blood cells.

According to Dr. Fathman, the results suggest that type 1 diabetes may

not result from genetic mutations but from differences in how normal

genes and gene variants are turned on and off during disease progression.

In addition to identifying altered genes that may indicate potential

avenues for therapeutic or preventive treatments, the authors also found

patterns of coordinated gene expression that may prove useful as

biomarkers of disease onset or progression.

The study was supported by the National Institute of Allergy and

Infectious Diseases, (NIAID) part of the National Institutes of Health.

(ANI)

Tissue- and age-specific changes in gene expression during disease

induction and progression in NOD mice.

Kodama K... et al... Fathman CG.

Clin Immunol. 2008 Sep 16. [Epub ahead of print]

Whole genome oligo-microarrays were used to characterize age-dependent

and tissue-specific changes in gene expression in pancreatic lymph

nodes, spleen, and peripheral blood cells, obtained from up to 8

individual NOD mice at 6 different time points (1.5 to 20 weeks of age),

compared to NOD.B10 tissue controls. " Milestone Genes " are genes whose

expression was significantly changed ( approximately 3 fold) as the

result of splicing or changes in transcript level. Milestone Genes were

identified among genes within type one diabetes (T1D) susceptibility

regions (Idd). Milestone Genes showing uniform patterns of changes in

expression at various time points were identified, but the patterns of

distribution and kinetics of expression were unique to each tissue.

Potential T1D candidate genes were identified among Milestone Genes

within Idd regions and/or hierarchical clusters. These studies

identified tissue- and age-specific changes in gene expression that may

play an important role in the inductive or destructive events of T1D.

PMID: 18801706