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Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP.

Publication ,  Journal Article
Czar, MJ; Kersh, EN; Mijares, LA; Lanier, G; Lewis, J; Yap, G; Chen, A; Sher, A; Duckett, CS; Ahmed, R; Schwartzberg, PL
Published in: Proc Natl Acad Sci U S A
June 19, 2001
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We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with infectious agents, recapitulated features of XLP. Infection of SAP- mice with lymphocyte choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell activation and IFN-gamma production, as well as a reduction of Ig-secreting cells. Anti-CD3-stimulated splenocytes from uninfected SAP- mice produced increased IFN-gamma and decreased IL-4, findings supported by decreased serum IgE levels in vivo. The Th1 skewing of these animals suggests that cytokine misregulation may contribute to phenotypes associated with mutation of SH2D1A/SAP.

Duke Scholars

Colin S Duckett
Author Colin S Duckett Pathology

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.131193098

ISSN

0027-8424

Publication Date

June 19, 2001

Volume

98

Issue

13

Start / End Page

7449 / 7454

Location

United States

Related Subject Headings

  • X Chromosome
  • Toxoplasmosis
  • T-Lymphocytes
  • Spleen
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Peptide Fragments
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice, Inbred Strains
  • Mice
 

Citation

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Chicago
ICMJE
MLA
NLM
Czar, M. J., Kersh, E. N., Mijares, L. A., Lanier, G., Lewis, J., Yap, G., … Schwartzberg, P. L. (2001). Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. Proc Natl Acad Sci U S A, 98(13), 7449–7454. https://doi.org/10.1073/pnas.131193098
Czar, M. J., E. N. Kersh, L. A. Mijares, G. Lanier, J. Lewis, G. Yap, A. Chen, et al. “Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP.” Proc Natl Acad Sci U S A 98, no. 13 (June 19, 2001): 7449–54. https://doi.org/10.1073/pnas.131193098.
Czar MJ, Kersh EN, Mijares LA, Lanier G, Lewis J, Yap G, et al. Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7449–54.
Czar, M. J., et al. “Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP.” Proc Natl Acad Sci U S A, vol. 98, no. 13, June 2001, pp. 7449–54. Pubmed, doi:10.1073/pnas.131193098.
Czar MJ, Kersh EN, Mijares LA, Lanier G, Lewis J, Yap G, Chen A, Sher A, Duckett CS, Ahmed R, Schwartzberg PL. Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7449–7454.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.131193098

ISSN

0027-8424

Publication Date

June 19, 2001

Volume

98

Issue

13

Start / End Page

7449 / 7454

Location

United States

Related Subject Headings

  • X Chromosome
  • Toxoplasmosis
  • T-Lymphocytes
  • Spleen
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Peptide Fragments
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice, Inbred Strains
  • Mice