Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas.

Holland AM, Góñez LJ, Naselli G, Macdonald RJ, Harrison LC
Diabetes. 2005 54 (9): 2586-95

PMID: 16123346 · DOI:10.2337/diabetes.54.9.2586

The homeodomain transcription factor Pdx1 is essential for pancreas development. To investigate the role of Pdx1 in the adult pancreas, we employed a mouse model in which transcription of Pdx1 could be reversibly repressed by administration of doxycycline. Repression of Pdx1 in adult mice impaired expression of insulin and glucagon, leading to diabetes within 14 days. Pdx1 repression was associated with increased cell proliferation predominantly in the exocrine pancreas and upregulation of genes implicated in pancreas regeneration. Following withdrawal of doxycycline and derepression of Pdx1, normoglycemia was restored within 28 days; during this period, Pdx1(+)/Ins(+) and Pdx(+)/Ins(-) cells were observed in association with the duct epithelia. These findings confirm that Pdx1 is required for beta-cell function in the adult pancreas and indicate that in the absence of Pdx1 expression, a regenerative program is initiated with the potential for Pdx1-dependent beta-cell neogenesis.

MeSH Terms (13)

Animals Diabetes Mellitus, Experimental Doxycycline Gene Expression Profiling Gene Expression Regulation Homeodomain Proteins Insulin Islets of Langerhans Mice Mice, Knockout Mice, Transgenic Regeneration Trans-Activators

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