We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
E2F-1-Deficient NOD/SCID Mice Developed Showing Decreased Saliva Production.
- Authors
HIKARU MATSUI-INOHARA; HIROSHI UEMATSU; TAKANORI NARITA; KEITARO SATOH; HIDEO YONEZAWA; KOICHIRO KURODA; TATSURO ITO; SAORI YONEDA; TAKETO KAWARAI; HIROSHI SUGIYA; HARUO WATANABE; HIDENOBU SENPUKU
- Abstract
The non-obese diabetic mouse (NOD) is the most characterized model used to study insulin-dependent type 1 diabetes mellitus (IDDM) and Sjögren's syndrome (SS). In a previous report, we found NOD.E2f1-1- 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.E2f1-1- 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 β 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.
- Publication
Experimental Biology & Medicine, 2009, Vol 234, Issue 12, p1525
- ISSN
1535-3702
- Publication type
Article
- DOI
10.3181/0905-RM-173