Functional effects of expression of wolframin-antisense transcripts in BRIN-BD11 beta-cells

Wolfram syndrome is a rare condition in which the pancreatic beta-cells of patients are selectively deleted during the early years of life by a non-autoimmune-mediated mechanism. The condition is associated with mutations in the gene encoding wolframin, suggesting that this protein exerts a critical, but currently unknown, function in beta-cells. We have used an antisense strategy to modulate the expression of wolframin in insulin-secreting BRIN-BD11 cells to study its function. Stably transfected clones were established expressing full-length human wolframin antisense transcripts. These cells exhibited a dramatic reduction in cell proliferation rate and changes in morphology, although insulin secretion was not modified. The results imply that wolframin expression is required to sustain normal rates of beta-cell proliferation.