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Exp Toxicol Pathol. 2014 Jul;66(4):203-9. doi: 10.1016/j.etp.2014.01.006. Epub 2014 Feb 28.

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.

Author information

1
Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan. Electronic address: fujiietk@chugai-pharm.co.jp.
2
Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
3
PharmaLogicals Research, Pte. Ltd., 11 Biopolis Way, #05-08/09 Helios, Singapore 138667, Singapore.
4
Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.

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.

KEYWORDS:

Adenomatous goiter; Human thyroid; Leakiness; NOG mouse; Thymic lymphoma; Transplantation

PMID:
24589354
DOI:
10.1016/j.etp.2014.01.006
[Indexed for MEDLINE]

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