title: Genomic organization and characterization of mouse SAP, the gene that is altered in X-linked lymphoproliferative disease.
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.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. cwu@caregroup.harvard.edu
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Sayos
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Howie
authors.forename: A
authors.initials: A
authors.lastname: Coyle
authors.forename: C
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D018076:DNA, Complementary; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012689:Sequence Homology, Nucleic Acid; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic; D014960:X Chromosome
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1