title: β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.
abstract: The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas.
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abdellatif
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Oishi
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Itagaki
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yunshin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hossam H
authors.initials: HH
authors.lastname: Shawki
authors.affiliation: Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Okita
authors.affiliation: Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Salah E
authors.initials: SE
authors.lastname: El-Morsy
authors.affiliation: Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mesbah A
authors.initials: MA
authors.lastname: El-Sayed
authors.affiliation: Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mahmoud B
authors.initials: MB
authors.lastname: Shoaib
authors.affiliation: Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Laboratory of Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.|Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki, Japan.|International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005934:Glucagon / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D051473:Maf Transcription Factors, Large / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D054392:Adipokines; C568466:C1qtnf12 protein, mouse; D007328:Insulin; D051473:Maf Transcription Factors, Large; D005934:Glucagon; D006836:Hydro-Lyases; C076392:pterin-4a-carbinolamine dehydratase