Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome.
Journal Article (Journal Article)
This study addresses the biological function of the p53-effector genes Gadd45a and p21 in the immune system. We find that Gadd45a is a negative regulator of T cell proliferation because, compared to wild-type cells, Gadd45a(-/-) T cells have a lower threshold of activation and proliferate to a greater extent following primary T cell receptor stimulation. Gadd45a(-/-) mice develop an autoimmune disease, similar to human systemic lupus erythematosus (SLE), characterized by high titers of anti-dsDNA, anti-ssDNA, and anti-histone autoantibodies, severe hematological disorders, autoimmune glomerulonephritis, and premature death. Here we show that the lack of both Gadd45a and p21 dramatically accelerates the development of autoimmunity observed in each individual single-gene disruption mutant, demonstrating that these genes play nonredundant roles in the immune response.
Full Text
Duke Authors
Cited Authors
- Salvador, JM; Hollander, MC; Nguyen, AT; Kopp, JB; Barisoni, L; Moore, JK; Ashwell, JD; Fornace, AJ
Published Date
- April 2002
Published In
Volume / Issue
- 16 / 4
Start / End Page
- 499 - 508
PubMed ID
- 11970874
Electronic International Standard Serial Number (EISSN)
- 1097-4180
International Standard Serial Number (ISSN)
- 1074-7613
Digital Object Identifier (DOI)
- 10.1016/s1074-7613(02)00302-3
Language
- eng