title: Histopathological characteristics of human non-tumor thyroid tissues in a long-term model of adenomatous goiter xenografts in the NOD/Shi-scid, IL-2Rγ(null) mouse.
abstract: There is a growing need for modeling the human thyroid to link data obtained from animals to humans because of its sensitivity to radiation exposure and endocrine disruption chemicals. In a scid mouse model produced by transplanting human thyroid tissues, leakiness and thymic lymphoma that occurs spontaneously in the scid mouse can complicate the interpretation of experimental results. Considering that the NOD.Cg-Prkdc(scid)Il2rg(tm1Sug)/Jic mouse (NOD/Shi-scid, IL-2Rγ(null) or NOG mouse) may be a better host because this strain has low incidence of leakiness and thymic lymphoma, we have evaluated the potential of a model that allows long-term observation of non-tumor human thyroid tissues in this mouse. We transplanted tissues of human adenomatous goiter into NOG mice and examined the tissues histopathologically. The morphology of human adenomatous goiter tissues was maintained from 24 to 44 weeks after transplantation in NOG mice with no noted differences between donor-matched tissues or the weeks after transplantation. The tissues expressed thyroglobulin protein and mRNA as well as thyroperoxidase. Endothelial cells originating from human were found in the transplanted tissues and were thought to be a characteristic of this model. The intactness of the tissues before transplantation was found to affect the rate of tissue engraftment. From the present results we have concluded that transplanted thyroid tissues in NOG mice maintain the histopathological characteristics of their origin for long terms. Therefore this model was thought feasible for toxicity evaluation.
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan. Electronic address: fujiietk@chugai-pharm.co.jp.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Fujii
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: PharmaLogicals Research, Pte. Ltd., 11 Biopolis Way, #05-08/09 Helios, Singapore 138667, Singapore.
authors.forename: Yu Jau
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: PharmaLogicals Research, Pte. Ltd., 11 Biopolis Way, #05-08/09 Helios, Singapore 138667, Singapore.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohnishi
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006042:Goiter / Q000276:immunology / Q000473:pathology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000276:immunology / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit
keywords: Adenomatous goiter; Human thyroid; Leakiness; NOG mouse; Thymic lymphoma; Transplantation