title: Histopathological characterization of renal tubular and interstitial changes in 5/6 nephrectomized marmoset monkeys (Callithrix jacchus).
abstract: Common marmosets (Callithrix jacchus) have become a useful animal model, particularly for development of biopharmaceuticals. While various renal failure models have been established in rodents, there is currently no acceptable model in marmosets. We analyzed the damaged renal tubules and tubulointerstitial changes (inflammation and fibrosis) of 5/6 nephrectomized (Nx) common marmosets by histopathological/immunohistochemical methods, and compared these findings to those in 5/6 Nx SD rats. In Nx marmosets and rats sacrificed at 5 and 13 weeks after Nx, variously dilated and atrophied renal tubules were seen in the cortex in common; however, the epithelial proliferating activity was much less in Nx marmosets. Furthermore, the degrees of inflammation and fibrosis seen in the affected cortex were more severe and massive in Nx marmosets with time-dependent increase. Interestingly, inflammation in Nx marmosets, of which degree was less in Nx rats, consisted of a large number of CD3-positive T cells and CD20-positive B cells (occasionally forming follicles), and a few CD68-positive macrophages. Based on these findings, lymphocytes might contribute to the progressive renal lesions in Nx marmosets. Fibrotic areas in Nx marmosets comprised myofibroblasts expressing vimentin and α-smooth muscle actin (α-SMA), whereas along with vimentin and α-SMA expressions, desmin was expressed in myofibroblasts in Nx rats. This study shows that there are some differences in renal lesions induced by Nx between marmosets and rats, which would provide useful, base-line information for pharmacology and toxicology studies using Nx marmosets.
authors.affiliation: Translational Research Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan; Veterinary Pathology, Osaka Prefecture University, Japan. Electronic address: yui.manabe@kyowa-kirin.co.jp.
authors.forename: Yui
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Translational Research Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamaguchi
authors.affiliation: Translational Research Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Myojo
authors.affiliation: Research Functions Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kimoto
authors.affiliation: Translational Research Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Imaizumi
authors.affiliation: Translational Research Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Takada
authors.affiliation: Research Functions Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sanada
authors.affiliation: Translational Research Unit, Research and Development Division, Kyowa Hakko Kirin, Co., Ltd., Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Takaba
authors.affiliation: Veterinary Pathology, Osaka Prefecture University, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000473:pathology*; D009392:Nephrectomy; D051381:Rats; D051436:Renal Insufficiency, Chronic
keywords: Immunohistochemistry; Lymphocytes; Marmoset monkey; Partial nephrectomy; Tubular damage; Tubulointerstitial change