Expression profile of MODY3/HNF-1alpha protein in the developing mouse pancreas.

  • Nammo T
  • Yamagata K
  • Hamaoka R
 et al. 
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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.

Author-supplied keywords

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

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Authors

  • T Nammo

  • K Yamagata

  • R Hamaoka

  • Q Zhu

  • T E Akiyama

  • F J Gonzalez

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