beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes

To study the late beta-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted specifically in beta cells. These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by...

Full description

Saved in:
Bibliographic Details
Published in:Genes & development 1998-06, Vol.12 (12), p.1763-1768
Main Authors: Ahlgren, U, Jonsson, J, Jonsson, L, Simu, K, Edlund, H
Format: Article
Language:English
Subjects:
Amyloid - analysis
Animals
Blood Glucose - metabolism
Cell Line
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Gene Expression Regulation
Genes - genetics
Glucagon - analysis
Glucose Intolerance
Glucose Tolerance Test
Glucose Transporter Type 2
Heterozygote
Homeodomain Proteins - analysis
Immunohistochemistry
Insulin - metabolism
Islet Amyloid Polypeptide
Islets of Langerhans - chemistry
Islets of Langerhans - growth & development
Islets of Langerhans - metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Mutant Strains
Monosaccharide Transport Proteins - analysis
Mutagenesis, Site-Directed
Phenotype
Research Communication
Trans-Activators - genetics
Trans-Activators - physiology
Transcriptional Activation - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To study the late beta-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted specifically in beta cells. These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-dependent manner suggesting that lowered IPF1/PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.12.12.1763