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


CONCLUSIONS
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.
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
T
T
Nammo
K
K
Yamagata
R
R
Hamaoka
Q
Q
Zhu
T E
TE
Akiyama
F J
FJ
Gonzalez
J
J
Miyagawa
Y
Y
Matsuzawa
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D015153:Blotting, Western; D019556:COS Cells; D004268:DNA-Binding Proteins; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000502:physiology*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D000090322:Homeobox Protein Nkx-2.2; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C496496:Hnf1b protein, mouse; D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta