title: Characterization of diabetic nephropathy in CaM kinase IIalpha (Thr286Asp) transgenic mice.
abstract: Detailed studies were performed on diabetic kidneys derived from transgenic mice overexpressing the mutant form (Thr286Asp) of Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaM kinase IIalpha) in pancreatic beta-cells. Kidney weight/body weight ratio, urinary albumin/creatinine ratio, serum BUN level, and mesangial/glomerular area ratio were all significantly higher in transgenic mice than in wild-type mice. cDNA microarray analysis revealed 17 up-regulated genes and 12 down-regulated genes in transgenic kidney. Among up-regulated genes, cyclin D2 (6.70-fold) and osteopontin (2.35-fold) were thought to play important roles in the progression of diabetic nephropathy. Transgenic glomeruli and tubular epithelial cells were strongly stained for osteopontin, a molecule which induces immune response. In quantitative real-time RT-PCR analyses, expressions of not only M1 macrophage marker genes but also M2 macrophage marker genes were elevated in renal cortex of transgenic mice. Overall results indicate that CaM kinase IIalpha (Thr286Asp) transgenic mice serve as an excellent model for diabetic nephropathy.
authors.affiliation: First Department of Internal Medicine, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Suzuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kato
authors.forename: Isao
authors.initials: I
authors.lastname: Usui
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oya
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Hiraga
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sasahara
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000378:metabolism; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013912:Threonine / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D012333:RNA, Messenger; C506896:Spp1 protein, mouse; C036763:monocyte-macrophage differentiation antigen; D053495:Osteopontin; D013912:Threonine; D001224:Aspartic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2