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Oct 31, 2008

Type 1 Diabetes May Be Based on Gene-Expression Signatures rather than Specific Variants

  • An immune response in type 1 diabetes could have less to do with having a distinct set of gene variants than how genes behave differently in patients compared to healthy people, according to researchers at the Stanford University School of Medicine.

    Using nonobese mice predisposed to type 1 diabetes and healthy counterparts, the team was surprised to notice that most genes in any given tissue of the diabetes-prone mice at any given time showed about the same expression levels as their disease-free controls.

    They did, however, identify time-dependent gene-expression signatures associated with certain clusters of genes. These genes seemed to participate in coordinated zigzags of swooping and soaring expression over time. The patterns varied from one tissue to the next and from time to time. In any given tissue at any given time, though, they were remarkably consistent.

    The scientists used two types of bioengineered mice that share a common genome with just one key difference. Nonobese diabetic (NOD) mice 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, known as NOD.B10, has the chromosomal segment containing the troublesome gene variant replaced with another, harmless version. NOD.B10 mice never get type 1 diabetes.

    The investigators used microarrays to compare the expression of 35,000 genes in each of the NOD mice with that of 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 and then 4, 8, 12, 16, and 20 weeks.

    The study is published in the November issue of Clinical Immunology.



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