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SATB1 Conditional Knockout Results in Sjögren’s Syndrome in Mice

Yuriko Tanaka, Takehiko Sotome, Akiko Inoue, Takanori Mukozu, Taku Kuwabara, Tetuo Mikami, Terumi Kowhi-Shigematsu and Motonari Kondo
J Immunol November 10, 2017, ji1700550; DOI: https://doi.org/10.4049/jimmunol.1700550
Yuriko Tanaka
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan;
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Takehiko Sotome
Department of Pediatrics, Toho University Omori Medical Center, Tokyo 143-8541, Japan;
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Akiko Inoue
Department of Otorhinolaryngology, Toho University Omori Medical Center, Tokyo 143-8541, Japan;Toho University Graduate School of Medicine, Tokyo 143-8540, Japan;
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Takanori Mukozu
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Tokyo 143-8541, Japan;
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Taku Kuwabara
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan;
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Tetuo Mikami
Department of Pathology, Toho University School of Medicine, Tokyo 143-8540, Japan; and
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Terumi Kowhi-Shigematsu
Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, CA 94143
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Motonari Kondo
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan;
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Abstract

Sjögren’s syndrome (SS) is an autoimmune disease in which exocrine tissues are affected by cellular and humoral immunity. As a result, the salivary and lacrimal glands of patients with SS are damaged, leading to xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Because experimental approaches to investigate SS pathogenesis in human patients are limited, development of a mouse model is indispensable for understanding the disease. In this study, we show that special AT-rich sequence binding protein-1 conditional knockout (SATB1cKO) mice, in which the SATB1 gene is specifically deleted from hematopoietic cells, develop SS by 4 wk of age, soon after weaning. Female mice presented an earlier onset of the disease than males, suggesting that female SATB1cKO mice are more susceptible to SS. T cell–dominant immune cell infiltration was observed in the salivary glands of 4 wk old SATB1cKO mice, and the frequency of B cells gradually increased as the mice aged. Consistently, levels of anti-SSA and anti-SSB Abs were increased around 8 wk of age, after salivary production reached its lowest level in SATB1cKO mice. These results suggest that SATB1cKO mice can be a novel SS model, in which the progression and characteristics of the disease resemble those of human SS.

Footnotes

  • This work was supported by a Japan Society for the Promotion of Science KAKENHI (JP24390121 to M.K. and Y.T., JP26670240 to M.K.); a Strategic Research Foundation Grant-aided Project for Private Schools at Heisei 26th (S1411015) from the Ministry of Education, Culture, Sports, Science and Technology to M.K.; a Research Promotion Grant from the Toho University Graduate School of Medicine (14-02 to M.K.); Project Research Grants from the Toho University School of Medicine (23-4, 26-22 and 27-10 to Y.T., 27-14 to A.I.); the Public Foundation of the Vaccination Research Center to M.K.; Initiative for Realizing Diversity in the Research Environment from the Japan Science and Technology Agency to Y.T.; a National Institutes of Health Grant (R37CA39681) to T.K.-S.; and a Grant-in Aid for Private University Research Branding Project from the Ministry of Education, Culture, Sports, Science and Technology to M.K.

  • Received April 18, 2017.
  • Accepted October 16, 2017.
  • Copyright © 2017 by The American Association of Immunologists, Inc.

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The Journal of Immunology: 200 (8)
The Journal of Immunology
Vol. 200, Issue 8
15 Apr 2018
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SATB1 Conditional Knockout Results in Sjögren’s Syndrome in Mice
Yuriko Tanaka, Takehiko Sotome, Akiko Inoue, Takanori Mukozu, Taku Kuwabara, Tetuo Mikami, Terumi Kowhi-Shigematsu, Motonari Kondo
The Journal of Immunology November 10, 2017, ji1700550; DOI: 10.4049/jimmunol.1700550

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SATB1 Conditional Knockout Results in Sjögren’s Syndrome in Mice
Yuriko Tanaka, Takehiko Sotome, Akiko Inoue, Takanori Mukozu, Taku Kuwabara, Tetuo Mikami, Terumi Kowhi-Shigematsu, Motonari Kondo
The Journal of Immunology November 10, 2017, ji1700550; DOI: 10.4049/jimmunol.1700550
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Print ISSN 0022-1767        Online ISSN 1550-6606