E2F-1-deficient NOD/SCID mice developed showing decreased saliva production.
The non-obese diabetic mouse (NOD) is the most characterized model used to study insulin-dependent type 1 diabetes mellitus (IDDM) and Sjoögren's syndrome (SS). In a previous report, we found NOD.E2f1(-/-) 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(+)CD25(+)) 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(-/-) 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 beta 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.
Matsui-Inohara
Hikaru
H
Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Uematsu
Hiroshi
H
Narita
Takanori
T
Satoh
Keitaro
K
Yonezawa
Hideo
H
Kuroda
Koichiro
K
Ito
Tatsuro
T
Yoneda
Saori
S
Kawarai
Taketo
T
Sugiya
Hiroshi
H
Watanabe
Haruo
H
Senpuku
Hidenobu
H
D000818:Animals; D001402:B-Lymphocytes; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D050687:E2F1 Transcription Factor; D007328:Insulin; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D012463:Saliva / Q000378:metabolism*; D012469:Salivary Glands / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory
D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D007328:Insulin; D051497:Receptor, Fibroblast Growth Factor, Type 2