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Type-1 diabetes not so much bad genes as good genes behaving badly, Stanford research shows
Date:10/30/2008

a faulty gene, Fathman's team looked for genes in the diabetic twin that act differently from the same genes in the other twin who doesn't get diabetes.

To do this, the Stanford researchers used two types of bioengineered mice that share a common genome, with just one key difference. So-called NOD mice (the acronym stands for "non-obese diabetic") are extremely likely to get type-1 diabetes and have an immune-related gene variant closely resembling the one predisposing humans to the disease. The other strain of mice, known as NOD.B10, has had its chromosomal segment containing the troublesome gene variant replaced with another, harmless version. NOD.B10 mice never get type-1 diabetes.

The Stanford team compared the activity level ("gene-expression," in scientific parlance) of each of the NOD mouse's genes - all 35,000 of them - with that of its counterpart in the NOD.B10 animals. To make these comparisons as meaningful as possible, the researchers assembled the mice into groups of three to 10 and took samples from various tissues from each group at 10 days of age, then four, eight, 12, 16 and 20 weeks, always comparing like tissues from one mouse strain to the next at the same stage of life. This required the use of a sophisticated but increasingly commonplace hybrid between a microscope slide and a computer chip - called a microarray - that can emit fluorescent signals corresponding to the activity levels of each of the mouse's genes.

By comparing the strength of the signal from any given gene from a particular tissue from NOD mice of a specific age to the corresponding gene in the NOD.B10 mice, it was possible to see which genes' activity levels were turned up, or dialed down, throughout the course of disease progression including the earliest stages. The NOD.B1O mice served as controls; by monitoring their tissues, scientists could determine any changes in gene expression that were mere
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Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

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