{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:43:20Z","timestamp":1777873400730,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:p>\n                    The non-obese diabetic mouse (NOD) is the most characterized model used to study insulin-dependent type 1 diabetes mellitus (IDDM) and Sjo\u00f6gren\u2019s syndrome (SS). In a previous report, we found NOD. E2f1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice show a greater progressive development to IDDM and SS compared to NOD mice. Our previous data indicated a progressive decrease in regulatory T cells (CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    ) and a decrease in the systemic secretion systems for insulin, and saliva was associated with the progression of IDDM and SS. Therefore, to define the mechanism of early-onset IDDM SS in E2F-1 deficient NOD mice required further investigation by producing E2F-1 deficient NOD\/SCID mice in which the T and B cells do not develop. The purpose here was to analyze the essential function of the E2F-1 molecule in the development of IDDM and SS; and the dysfunction of the pancreas islet and salivary gland in the NOD background using NOD\/SCID mice. We produced NOD\/SCID. E2f1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice using homologous recombination; determined diabetes development; measured saliva and insulin production; and performed a histological analysis. The deficient mice showed a decreasing volume of saliva; no infiltration of lymphocytes into salivary glands; no development of diabetes; and no protein localization of FGFR-2b in the ducts of the salivary gland that regulates submandibular gland proliferation and morphogenesis. Therefore, we considered a deficiency in E2F-1 induces a decrease in regulatory T cells and an increase in auto-reactive T cells; however, the E2F-1 deficiency is not associated with T and B cells-independent dysfunction of pancreatic \u03b2 cell in insulin secretion. Further, the E2F-1 deficiency is associated with T and B cells-independent dysfunction of the salivary gland exhibits a decrease in saliva production volume. We suggest E2F-1 may be also associated with the differentiation of exocrine cells in the duct where FGFR-2b is expressed in the salivary gland. The E2F-1 deficient NOD\/SCID mouse model is useful for showing the development of the salivary gland; and is also useful for various experiments in humanized mice.\n                  <\/jats:p>","DOI":"10.3181\/0905-rm-173","type":"journal-article","created":{"date-parts":[[2009,11,24]],"date-time":"2009-11-24T13:57:49Z","timestamp":1259071069000},"page":"1525-1536","source":"Crossref","is-referenced-by-count":15,"title":["E2F-1-Deficient NOD\/SCID Mice Developed Showing Decreased Saliva Production"],"prefix":"10.3389","volume":"234","author":[{"given":"Hikaru","family":"Matsui-Inohara","sequence":"first","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Narita","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keitaro","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Yonezawa","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuro","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saori","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taketo","family":"Kawarai","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Sugiya","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenobu","family":"Senpuku","sequence":"additional","affiliation":[{"name":"Department of Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Bacteriology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Physiology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan; Division of Medical Microbiology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; and Department of Bacteriology, Nihon University School of Dentistry, Tokyo 101..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2009,12,1]]},"reference":[{"key":"bibr-R1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80195-8"},{"key":"bibr-R2","unstructured":"Hattori M, Yamato E, Itoh N, Senpuku H, Fujisawa T, Yoshino M, Fukuda M, Matsumoto E, Toyonaga T, Nakagawa I, Petruzzelli M, McMurray A, Weiner H, Sagai T, Moriwaki K, Shiroishi T, Maron R, Lund T. 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