title: Establishment of inducible cAMP early repressor transgenic fibroblasts             in a porcine model of human type 1 diabetes mellitus.
abstract: Diabetes mellitus is a metabolic disease caused by impaired insulin secretion             from the pancreatic β cells and increased insulin resistance in peripheral tissues.             Recently, the overexpression of inducible cyclic AMP (cAMP) early repressor (ICER)             Iγ in rodent pancreatic β cells was found to induce insulin deficiency and glucagon             overproduction similar to that found in human diabetes mellitus. ICER Iγ with             only a DNA binding domain interrupts the transcriptional regulation of the cAMP             responsive element-binding protein (CREB) target genes. Based on this information,             we hypothesized that the overexpression of ICER Iγ, the most powerful competitor             to CREB, could be useful for generating a pig model of diabetes. First, we evaluated             the promoter activities of the human insulin gene for the β cell-specific overexpression             of ICER Iγ in the pig pancreas. The maximum promoter activity region [-1,431 nucleotides             (nt) to +1 nt, +1 = the transcriptional start site] of the insulin gene presented             an activity level 3-fold higher than a promoterless construct. Second, ICER Iγ             overexpression controlled by this promoter region significantly blocked the glucose-mediated             insulin transcription, such as that regulated by the viral promoter in the pancreatic             β cell line, MIN6. This suggests that the human insulin promoter may facilitate             the overexpression of ICER Iγ in porcine pancreatic β cells. In addition, the             overexpression of ICER Iγ in porcine β cells may induce human-like type 1 diabetes             mellitus in pigs. In the present study, we generated transgenic fibroblasts containing             ICER Iγ cDNA controlled by the human insulin promoter, as well as two screening             markers, the green fluorescence protein and the neomycin resistance gene. These             fibroblasts may provide a source for somatic cell nuclear transfer to generate             a pig model that mimics human diabetes mellitus.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology,                     College of Veterinary Medicine, Chungbuk National University, Cheongju,                     Chungbuk 361-763, Republic of Korea.
authors.forename: Eui-Man
authors.initials: EM
authors.lastname: Jung
authors.forename: Yu-Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Geun-Shik
authors.initials: GS
authors.lastname: Lee
authors.forename: Sang-Hwan
authors.initials: SH
authors.lastname: Hyun
authors.forename: Woo-Suk
authors.initials: WS
authors.lastname: Hwang
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000818:Animals; D002460:Cell Line; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D023061:Gene Order; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D013552:Swine; D019076:Transgenes
chemical_list: D007328:Insulin; D051786:Cyclic AMP Response Element Modulator