title: Phenotypic differences between mice deficient in XIAP and SAP, two factors targeted in X-linked lymphoproliferative syndrome (XLP).
abstract: Mutations in the X-linked inhibitor of apoptosis (XIAP) have recently been identified in patients with the rare genetic disease, X-linked lymphoproliferative syndrome (XLP), which was previously thought to be solely attributable to mutations in a distinct gene, SAP. To further understand the roles of these two factors in the pathogenesis of XLP, we have compared mice deficient in Xiap with known phenotypes of Sap-null mice. We show here that in contrast to Sap-deficient mice, animals lacking Xiap have apparently normal NKT cell development and no apparent defect in humoral responses to T cell-dependent antigens. However, Xiap-deficient cells were more susceptible to death upon infection with the murine herpesvirus MHV-68 and gave rise to more infectious virus. These differences could be rescued by restoration of XIAP. These data provide insight into the differing roles of XIAP and SAP in the pathogenesis of XLP.
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
authors: Julie M
authors: JM
authors: Rumble
authors: Karolyn A
authors: KA
authors: Oetjen
authors: Paul L
authors: PL
authors: Stein
authors: Pamela L
authors: PL
authors: Schwartzberg
authors: Bethany B
authors: BB
authors: Moore
authors: Colin S
authors: CS
authors: Duckett
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006564:Herpesviridae / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein