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Molecular and Cellular Biology, December 2005, p. 11030-11034, Vol. 25, No. 24
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.24.11030-11034.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Reexamination of the Role of Ubiquitin-Like Modifier ISG15 in the Phenotype of UBP43-Deficient Mice

Klaus-Peter Knobeloch,1 Olaf Utermöhlen,2 Agnes Kisser,1 Marco Prinz,3 and Ivan Horak1*

Abteilung für Molekulare Genetik, Institut für Molekulare Pharmakologie, and Charité Universitätsmedizin, Berlin, Germany,1 Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Universität Köln, Cologne, Germany,2 Institut für Neuropathologie, Universität Göttingen, Göttingen, Germany3

Received 15 July 2005/ Accepted 21 September 2005

UBP43/USP18 was described as a specific protease that removes conjugated ubiquitin-like modifier ISG15 from target proteins. The severe phenotype of UBP43–/– mice characterized by premature death, brain cell injury, and deregulated STAT1 signaling was ascribed to an enhanced conjugation of ISG15. In contrast, no phenotypic changes were detected in ISG15–/– mice. To verify the role of ISG15 in the phenotype of UBP43–/– mice, we employed mice deficient for both ISG15 and UBP43. Here, we show that the phenotype of UBP43–/– mice was not rescued by the absence of ISG15, as evident from unchanged mortality, neurological symptoms, and occurrence of hydrocephalus. Also, the reported hypersensitivity of UBP43–/– mice to an interferon inducer, poly(I · C), was ISG15 independent. Furthermore, no evidence for a role of ISG15 in the modulation of STAT1 signaling or in the resistance against lymphocytic choriomeningitis virus and vesicular stomatitis virus was found. Presented results clearly demonstrate that the phenotypic alterations of UBP43–/– mice are not caused by the lack of ISG15 deconjugation and must be due to another, non-ISG15-mediated molecular mechanism.

* Corresponding author. Mailing address: Institute of Molecular Pharmacology, Department of Molecular Genetics, Krahmerstr. 6, 12207 Berlin, Germany. Phone: 49 3084371911. Fax: 49 3084371922. E-mail: horak{at}fmp-berlin.de.

Molecular and Cellular Biology, December 2005, p. 11030-11034, Vol. 25, No. 24
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.24.11030-11034.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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