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Diabetologia

, Volume 45, Issue 8, pp 1142–1153 | Cite as

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

  •  T. Nammo
  •  K. Yamagata
  •  R. Hamaoka
  •  Q. Zhu
  •  T. Akiyama
  •  F. Gonzalez
  •  J. Miyagawa
  •  Y. Matsuzawa
Article

Heading

Abstract

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

Methods. Double immunofluorescence staining was carried out for HNF-1α 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 α mutant mice.

Results. HNF-1α was expressed by both endocrine and exocrine cells of the pancreas. Double immunofluorescence staining showed that HNF-1α was expressed in the nuclei of alpha cells, beta cells, delta cells, and pancreatic polypeptide (PP) cells. HNF-1α 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-1α on E15.5. Most of the Pax6-, Isl1-, or PDX-1-positive cells showed co-expression of HNF-1α. However, HNF-1α 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-1α. Expression of PDX-1 did not change in the beta cells of pre-diabetic HNF-1 α (–/–) mice, but expression was markedly decreased in the diabetic stage.

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

HNF-1α transcription factor development mouse pancreas 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  •  T. Nammo
    • 2
  •  K. Yamagata
    • 1
  •  R. Hamaoka
    • 2
  •  Q. Zhu
    • 2
  •  T. Akiyama
    • 3
  •  F. Gonzalez
    • 3
  •  J. Miyagawa
    • 2
  •  Y. Matsuzawa
    • 2
  1. 1.Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
  2. 2.Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan
  3. 3.Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

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