title: Functional effects of expression of wolframin-antisense transcripts in BRIN-BD11 beta-cells.
abstract: 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.
authors.affiliation: School of Life Sciences, Keele University, Staffs ST5 5BG, UK.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: McBain
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics) / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000254:growth & development / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D016375:Antisense Elements (Genetics); D007328:Insulin; D008565:Membrane Proteins; C114987:wolframin protein; D004247:DNA