Oncotarget

Research Papers:

Overexpression of TSC-22 (transforming growth factor- β-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice

Daisuke Uchida _, Hitoshi Kawamata, Fumie Omotehara, Yoshihiro Miwa, Hideki Horiuchi, Tadashi Furihata, Masatsugu Tachibana and Takahiro Fujimori

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Oncotarget. 2016; 7:14310-14323. https://doi.org/10.18632/oncotarget.7308

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Abstract

Daisuke Uchida1,*, Hitoshi Kawamata1,*, Fumie Omotehara2,*, Yoshihiro Miwa3, Hideki Horiuchi2, Tadashi Furihata2, Masatsugu Tachibana2, Takahiro Fujimori2

1Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan

2Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan

3Department of Pharmacology, Institute of Basic Medical Sciences, The University of Tsukuba, Tsukuba, Ibaragi, Japan

*These authors have contributed equally to this work

Correspondence to:

Daisuke Uchida, e-mail: [email protected]

Keywords: TSC-22, Tg-mice, obesity, splenic abnormality, B cell lymphoma

Received: November 17, 2015     Accepted: January 29, 2016     Published: February 10, 2016

ABSTRACT

In this study, we generated transgenic (Tg) mice, which overexpressed transforming growth factor (TGF)-β stimulated clone-22 (TSC-22), and investigate the functional role of TSC-22 on their development and pathogenesis. We obtained 13 Tg-founders (two mice from C57BL6/J and 11 mice from BDF1). Three of 13 Tg-founders were sterile, and the remaining Tg-founders also could generate only a limited number of the F1 generation. We obtained 32 Tg-F1 mice. Most of the Tg-mice showed marked obesity. Histopathological examination could be performed on 31 Tg-mice; seventeen mice died by some disease in their entire life and 14 mice were killed for examination. Most of the Tg-mice examined showed splenic abnormality, in which marked increase of the megakaryocytes, unclearness of the margin of the red pulp and the white pulp, and the enlargement of the white pulp was observed. B cell lymphoma was developed in 10 (71%) of 14 disease-died F1 mice. These results indicate that constitutive over-expression of TSC-22 might disturb the normal embryogenesis and the normal lipid metabolism, and induce the oncogenic differentiation of hematopoietic cells.


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