Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome.

Published

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

Pubmed Central ID

  • 11970874

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(02)00302-3

Language

  • eng

Conference Location

  • United States