Genomic organization and characterization of mouse SAP, the gene that is altered in X-linked lymphoproliferative disease

Immunogenetics. 2000 Aug;51(10):805-15. doi: 10.1007/s002510000215.

Abstract

X-linked lymphoproliferative (XLP) disease is a fatal immunological disorder that renders the immune system unable to respond effectively to Epstein-Barr virus (EBV) infection. The gene that encodes a protein termed SAP or SH2D1A is either deleted or mutated in XLP patients, resulting in uncontrolled B- and T-cell proliferation upon EBV infection. Here, we report the cloning and characterization of the mouse SAP gene. It is localized on the mouse X chromosome and comprises four exons spanning approximately 25 kb. Its expression appears to be restricted to T lymphocytes. Whereas a high level of SAP expression is observed in Thl cells, only small amounts are detectable in Th2 cells. Moreover, SAP expression is down-regulated upon in vitro activation of T cells, including CD4+, CD8+ single-positive T cells, and Thl and Th2 cells. This study provides valuable information for in-depth genetic and biochemical analysis of the function of SAP in the immune system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Base Sequence
  • Carrier Proteins / genetics*
  • Chromosome Mapping
  • DNA, Complementary
  • Down-Regulation
  • Glycoproteins / genetics
  • Humans
  • Immunoglobulins / genetics
  • Intracellular Signaling Peptides and Proteins*
  • Lymphocyte Activation
  • Lymphoproliferative Disorders / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Receptors, Cell Surface
  • Sequence Homology, Nucleic Acid
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • T-Lymphocytes / metabolism
  • Transcription, Genetic
  • X Chromosome*

Substances

  • Antigens, CD
  • Carrier Proteins
  • DNA, Complementary
  • Glycoproteins
  • Immunoglobulins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • SH2D1A protein, human
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family Member 1

Associated data

  • GENBANK/AF154503
  • GENBANK/AF154504
  • GENBANK/AF154505