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

Jesus M. Salvador, M. Christine Hollander, Anh Thu Nguyen, Jeffrey B. Kopp, Laura Barisoni-Thomas, Jodene K. Moore, Jonathan D. Ashwell, Albert J. Fornace

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalImmunity
Volume16
Issue number4
DOIs
StatePublished - May 7 2002
Externally publishedYes

Fingerprint

p53 Genes
T-Lymphocytes
Premature Mortality
Glomerulonephritis
T-Cell Antigen Receptor
Autoimmunity
Systemic Lupus Erythematosus
Autoantibodies
Histones
Genes
Autoimmune Diseases
Immune System
Cell Proliferation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Salvador, J. M., Hollander, M. C., Nguyen, A. T., Kopp, J. B., Barisoni-Thomas, L., Moore, J. K., ... Fornace, A. J. (2002). Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity, 16(4), 499-508. https://doi.org/10.1016/S1074-7613(02)00302-3

Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. / Salvador, Jesus M.; Hollander, M. Christine; Nguyen, Anh Thu; Kopp, Jeffrey B.; Barisoni-Thomas, Laura; Moore, Jodene K.; Ashwell, Jonathan D.; Fornace, Albert J.

In: Immunity, Vol. 16, No. 4, 07.05.2002, p. 499-508.

Research output: Contribution to journalArticle

Salvador, JM, Hollander, MC, Nguyen, AT, Kopp, JB, Barisoni-Thomas, L, Moore, JK, Ashwell, JD & Fornace, AJ 2002, 'Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome', Immunity, vol. 16, no. 4, pp. 499-508. https://doi.org/10.1016/S1074-7613(02)00302-3
Salvador, Jesus M. ; Hollander, M. Christine ; Nguyen, Anh Thu ; Kopp, Jeffrey B. ; Barisoni-Thomas, Laura ; Moore, Jodene K. ; Ashwell, Jonathan D. ; Fornace, Albert J. / Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. In: Immunity. 2002 ; Vol. 16, No. 4. pp. 499-508.
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