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Expression profile of MODY3/HNF-1alpha protein in the developing mouse pancreas
T Nammo1, K Yamagata, R Hamaoka
1Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
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.
Insights
Hepatocyte nuclear factor (HNF)-1alpha is expressed in developing mouse pancreas endocrine and exocrine cells. This suggests HNF-1alpha plays a role in pancreatic development.
Area of Science:
- Developmental Biology
- Endocrinology
- Genetics
Background:
- MODY3, a subtype of monogenic diabetes, is caused by HNF-1alpha mutations.
- The expression pattern of HNF-1alpha in the normal pancreas is not well-defined.
Purpose of the Study:
- To investigate the protein expression profile of HNF-1alpha in the developing mouse pancreas.
Main Methods:
- Double immunofluorescence staining was used to detect HNF-1alpha alongside pancreatic hormones and transcription factors (PDX-1, Pax6, Isl1, Nkx2.2).
- HNF-1alpha expression was also examined in beta cells of HNF-1alpha mutant mice.
Main Results:
- HNF-1alpha is expressed in both endocrine (alpha, beta, delta, PP cells) and exocrine pancreatic cells starting from embryonic day 10.5.
- Co-expression of HNF-1alpha was observed with Pax6, Isl1, and PDX-1, but not consistently with Nkx2.2.
- PDX-1 expression decreased in diabetic HNF-1alpha (-/-) mice, while other factors remained normal in mutant beta cells.
Conclusions:
- HNF-1alpha is expressed throughout the developing pancreas, in both endocrine and exocrine lineages.
- Its expression alongside other key transcription factors suggests a crucial role for HNF-1alpha in pancreatic development.