title: Dysfunction of erythropoietin-producing interstitial cells in the kidneys of ICR-derived glomerulonephritis (ICGN) mice.
abstract: Anemia is a major secondary symptom in chronic renal disorder (CRD), but the precise cause of insufficient production of erythropoietin (EPO) remains unclear owing to the controversial localization of EPO-producing cells in the kidneys. The ICR-derived glomerulonephritis (ICGN) mouse, a new hereditary nephrotic mouse, is an appropriate model of anemia associated with CRD. By using an amplified in situ hybridization technique, we detected and counted the renal EPO-producing cells under both normoxic and hypoxic conditions. The expression levels of renal EPO mRNA were quantified and oxygen gradients were also assessed immunohistochemically. Amplified in situ hybridization clarified that EPO-producing cells were peritubular interstitial cells in the middle region of renal cortex in both ICR and ICGN mice. Hypoxia (7% O2) induced low oxygen tension in proximal tubular epithelial cells of renal cortex, and increased the expression of EPO mRNA and the number of EPO-producing cells in both ICR and ICGN mice. However, hypoxia did not increase the serum EPO levels in ICGN mice. The ICGN mouse is a good model for anemia associated with CRD, and the suppression of EPO protein production in the renal EPO-producing cells is considered to be a potential cause of anemia associated with CRD.
authors.affiliation: Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Yamaguchi-Yamada
authors.forename: Noboru
authors.initials: N
authors.lastname: Manabe
authors.forename: Minako
authors.initials: M
authors.lastname: Kiso
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Goto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Mori
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Sakata
authors.forename: Sayuri
authors.initials: S
authors.lastname: Anan
authors.forename: Masaya
authors.initials: M
authors.lastname: Nagao
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
mesh_terms: D000704:Analysis of Variance; D000740:Anemia / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology* / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D004921:Erythropoietin