Cathepsin K-Cre causes unexpected germline deletion of genes in mice

Crystal L. Winkeler, Raleigh D. Kladney, Leonard B. Maggi, Jason D. Weber

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Osteoclasts are terminally differentiated cells that attach to bone and secrete proteases to degrade the bone matrix. The primary protease responsible for the degradation of the organic component of the bone matrix is Cathepsin K, which was largely thought to be unique to osteoclasts. Given its apparent selective expression in osteoclasts, the Cathepsin K promoter has been engineered to drive the expression of Cre recombinase in mice and has been the most relevant tool for generating osteoclast-specific gene loss. In an effort to understand the role of the ARF tumor suppressor in osteoclasts, we crossed Arf fl/fl mice to CtskCre/+ mice, which unexpectedly resulted in the germline loss of Arf. We subsequently confirmed Cre activity in gametes by generating CtskCre/+; Rosa+ mice. These results raise significant concerns regarding in vivo bone phenotypes created using CtskCre/+ mice and warrant further investigation into the role of Cathepsin K in gametes as well as alternative tools for studying osteoclast-specific gene loss in vivo.

Original languageEnglish
Article numbere42005
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 31 2012

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