title: Overexpression of TSC-22 (transforming growth factor- β-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uchida
authors.affiliation: Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawamata
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Omotehara
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, The University of Tsukuba, Tsukuba, Ibaragi, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miwa
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horiuchi
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Furihata
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimori
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000502:physiology*; D013154:Spleen / Q000378:metabolism / Q000473:pathology*
chemical_list: D012097:Repressor Proteins; C490983:Tgfb1i4 protein, mouse
keywords: B cell lymphoma; TSC-22; Tg-mice; obesity; splenic abnormality