The results, said Fathman, were surprising. Most genes in any given tissue of the diabetes-prone NOD mice at any given time showed about the same activity levels as their disease-free NOD.B10 counterparts. But in each tissue the scientists monitored, certain clusters of genes in NOD-mice - including many genes never previously identified as germane to the disease process - seemed to participate in coordinated zigzags of swooping and soaring expression over time, when compared with their healthy NOD-B10 "twins." These patterns varied from one tissue to the next and from time to time. But in any given tissue at any given time, they were remarkably consistent.
These time-dependent gene-expression "signatures" could be observed in the NOD mice's peripheral blood, for example, well before the mice began to show characteristic signs of diabetes such as hyperglycemia. Fathman said preliminary work done in his lab indicates an exquisite similarity to the gene-expression signatures found in the blood of humans with type-1 diabetes well before the onset of symptoms.
This finding may provide an early warning for pre-diabetics, Fathman said. "We need to know that people are on their way to diabetes before they get hyperglycemic or, better, even before their insulin-producing pancreas cells have taken a hit." Plus, the newly identified genes in these clusters with orchestrated, disease-associated activity changes may, in their own right, point the way to new therapies, he said.
One matter still unresolved is exactly why a diabetic identical twin's
genes began acting differently from the non-diabetic twin's in the first
place. Fathman believes this may be due to random differences in exactly
which part of some invading or internal pathoge
|Contact: Bruce Goldman|
Stanford University Medical Center