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

• Published in: Diabetologia Vol. 45; no. 8; p. 1142
• Main Authors: Nammo, T, Yamagata, K, Hamaoka, R, Zhu, Q, Akiyama, T, Gonzalez, F, Miyagawa, J, Matsuzawa, Y
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.08.2002
• Subjects: Antibodies; Diabetes; Embryos; Internal medicine; Medicine; Pancreas; Peptides; Proteins; Transcription factors; Transgenic animals; United States > US; Japan
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-002-0892-8

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-1α 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-1α (-/-) 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.