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Molecular and Cellular Biology, May 2001, p. 3604-3608, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3604-3608.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Characterization of XIAP-Deficient Mice

Helena Harlin,1 Stephanie Birkey Reffey,2 Colin S. Duckett,2 Tullia Lindsten,3 and Craig B. Thompson3,*

Committee on Immunology, Department of Medicine, University of Chicago, Chicago, Illinois 606371; Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922; and Departments of Cancer Biology and Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 191043

Received 11 December 2000/Returned for modification 20 December 2000/Accepted 15 February 2001

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.

* Corresponding author. Mailing address: Abramson Family Cancer Research Institute, Room 450, BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160. Phone: (215) 746-5515. Fax: (215) 746-5511. E-mail: craig{at}mail.med.upenn.edu.

Molecular and Cellular Biology, May 2001, p. 3604-3608, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3604-3608.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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