Characterization of XIAP-deficient mice

The inhibitor of apoptosis protein (IAP) family consists of a number of evo lutionarily conserved proteins that function to inhibit programmed cell dea th. S-linked L-IP (SL-IP) was clotted due to its sequence homolog with othe r family members and has previously been shown to prevent apoptosis by bind ing to active caspases 3, 7, and 9 in vitro. XIAP transcripts can be found in a variety of tissues, anti the protein levels are regulated both transcr iptionally and posttranscriptionally. To better understand tile function of XIAP in normal cells, tr;e generated mice deficient in XIAP through homolo gous gene targeting. The resulting mice were viable, and histopathological analysis did not reveal any differences between XIAP-deficient and wild-typ e mice. We were unable to detect any defects in induction of caspase-depend ent or -independent apoptosis in cells from the gene-targeted mice. One cha nge 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 w hen XIAP expression is lost. The changes in c-IAP1 and c-IAP2 expression ma y provide functional compensation for loss of XIAP during development or in the induction of apoptosis.