title: Characterization of XIAP-deficient mice.
abstract: The inhibitor of apoptosis protein (IAP) family consists of a number of evolutionarily conserved proteins that function to inhibit programmed cell death. X-linked IAP (XIAP) was cloned due to its sequence homology with other family members and has previously been shown to prevent apoptosis by binding to active caspases 3, 7, and 9 in vitro. XIAP transcripts can be found in a variety of tissues, and the protein levels are regulated both transcriptionally and posttranscriptionally. To better understand the function of XIAP in normal cells, we generated mice deficient in XIAP through homologous gene targeting. The resulting mice were viable, and histopathological analysis did not reveal any differences between XIAP-deficient and wild-type mice. We were unable to detect any defects in induction of caspase-dependent or -independent apoptosis in cells from the gene-targeted mice. One change was observed in cells derived from XIAP-deficient mice: the levels of c-IAP1 and c-IAP2 protein were increased. This suggests that there exists a compensatory mechanism that leads to upregulation of other family members when XIAP expression is lost. The changes in c-IAP1 and c-IAP2 expression may provide functional compensation for loss of XIAP during development or in the induction of apoptosis.
authors: Committee on Immunology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
authors: H
authors: H
authors: Harlin
authors: S B
authors: SB
authors: Reffey
authors: C S
authors: CS
authors: Duckett
authors: T
authors: T
authors: Lindsten
authors: C B
authors: CB
authors: Thompson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics*; D051636:X-Linked Inhibitor of Apoptosis Protein; D016335:Zinc Fingers
chemical_list: D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein