Mice deficient in the X-linked lymphoproliferative disease gene sap exhibit increased susceptibility to murine gammaherpesvirus-68 and hypo-gammaglobulinemia

Luo Yin, Umaima Al-Alem, Jun Liang, Wei Min Tong, Cuiling Li, Manuela Badiali, Jean Jacques Médard, Janos Sumegi, Zhao Qi Wang, Giovanni Romeo

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

X-linked lymphoproliferative disease is characterized by immune dysregulation and uncontrolled lymphoproliferation on exposure to Epstein-Barr virus (EBV). This disease has been attributed to mutations in the SAPgene (also denominated as SH2D1A or DSHP). To delineate the role of SAP in the pathophysiology of X-linked lymphoproliferative disease, a strain of sap-deficient mice has been generated by deleting exon 2 of the gene. After infection with murine gammaherpesvirus-68, which is homologousto EBV, the mutant mice exhibit more vigorous CD8+ T cell proliferation and more disseminated lymphocyte infiltration compared to their wild-type littermates. Chronic tissue damage and hemophagocytosis were evident in sap-deficient mice but not in their wild-type littermates. Concordantly, murine gammaherpesvirus-68 reactivation was observed in sap-deficient mice, indicating an impaired control of the virus. Notably, IgE deficiency and decreased serum IgG level were observed in mutant mice prior to and after murine gammaherpesvirus-68 infection, which reproduces hypogammaglobulinemia in X-linked lymphoproliferative disease patients. This mouse model will therefore be a useful tool for dissecting the various phenotypes of X-linked lymphoproliferative disease.

Original languageEnglish (US)
Pages (from-to)446-455
Number of pages10
JournalJournal of Medical Virology
Volume71
Issue number3
DOIs
StatePublished - Nov 1 2003

Keywords

  • Immunodeficiency
  • Immunoglobulin production
  • T lymphocyte proliferation
  • sap knockout

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Yin, L., Al-Alem, U., Liang, J., Tong, W. M., Li, C., Badiali, M., Médard, J. J., Sumegi, J., Wang, Z. Q., & Romeo, G. (2003). Mice deficient in the X-linked lymphoproliferative disease gene sap exhibit increased susceptibility to murine gammaherpesvirus-68 and hypo-gammaglobulinemia. Journal of Medical Virology, 71(3), 446-455. https://doi.org/10.1002/jmv.10504