Expression Profile of MODY3/HNF-1alpha Protein in the Developing Mouse Pancreas

Diabetologia. 2002 Aug;45(8):1142-53. doi: 10.1007/s00125-002-0892-8. Epub 2002 Jun 28.

Abstract

Aims/hypothesis: One subtype of MODY (MODY3) results from the heterozygous mutation of a hepatocyte nuclear factor (HNF)-1alpha. The pattern of HNF-1alpha expression in the normal pancreas has not been determined. This study aimed to clarify the profile of HNF-1alpha protein expression in the developing mouse pancreas.

Methods: Double immunofluorescence staining was carried out for HNF-1alpha and pancreatic hormones or transcription factors (PDX-1, Pax6, Isl1, and Nkx2.2). The expression of these transcription factors was also studied in the beta cells of HNF-1 alpha mutant mice.

Results: HNF-1alpha was expressed by both endocrine and exocrine cells of the pancreas. Double immunofluorescence staining showed that HNF-1alpha was expressed in the nuclei of alpha cells, beta cells, delta cells, and pancreatic polypeptide (PP) cells. HNF-1alpha was first detected in most pancreatic epithelial cells on embryonic day 10.5 (E10.5), and hormone-positive endocrine cells and amylase-positive cells expressed HNF-1alpha on E15.5. Most of the Pax6-, Isl1-, or PDX-1-positive cells showed co-expression of HNF-1alpha. However, HNF-1alpha immunoreactivity was not observed in 36.0% of Nkx2.2-positive cells. Expression of Nkx2.2, Isl1 and Pax6 seemed to be normal in the beta cells of transgenic mice with dominant negative overexpression of HNF-1alpha. Expression of PDX-1 did not change in the beta cells of pre-diabetic HNF-1 alpha (-/-) mice, but expression was markedly decreased in the diabetic stage.

Conclusion/interpretation: HNF-1alpha is expressed by both endocrine cells and exocrine cells of the pancreas from the foetal stage along with other transcription factors, so HNF-1alpha might play a role during development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn / growth & development*
  • Animals, Newborn / metabolism*
  • Blotting, Western
  • COS Cells
  • DNA-Binding Proteins*
  • Embryonic and Fetal Development
  • Fetus / physiology*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins*
  • Pancreas / embryology*
  • Pancreas / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Hnf1b protein, mouse
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta