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Generation of aggrecan‐CreERT2 knockin mice for inducible Cre activity in adult cartilage
Author(s) -
Henry Stephen P.,
Jang ChuanWei,
Deng Jian Min,
Zhang Zhaoping,
Behringer Richard R.,
de Crombrugghe Benoit
Publication year - 2009
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20564
Subject(s) - cre recombinase , aggrecan , biology , cartilage , microbiology and biotechnology , endochondral ossification , extracellular matrix , gene , transgene , genetically modified mouse , anatomy , genetics , pathology , osteoarthritis , medicine , alternative medicine , articular cartilage
The function of cartilage in the adult is dependent on a host of regulatory molecules such as growth factors, extracellular matrix, enzymes, signaling molecules, and transcription factors. However, germline mutations in some genes that are expressed in adult cartilage lead to embryonic or perinatal lethality. To examine the function of these and other genes postnatally, we have generated a targeted mouse by homologous recombination that “knocks in” the inducible Cre recombinase construct, CreERT2, in the 3′ untranslated region of the endogenous mouse aggrecan gene ( Agc1 tm (IRES‐creERT2) ). The properties and efficiency of the inducible cre recombinase were tested by examining X‐gal staining of tissues from embryos as well as growing and adult Agc1 tm (IRES‐creERT2)/+ ; Rosa 26R mice. These mice were injected with the inducer, tamoxifen, at different time points during embryonic development and postnatally up to 6 months of age. Strong X‐gal staining was observed in growth plate and articular cartilage as well as the fibrocartilage of meniscus, trachea, and intervertebral discs reproducing the pattern of endogenous aggrecan gene expression. In conclusion, we have generated a mouse model in which genes implicated in cartilage degenerative diseases can be inactivated in a spatial and temporal fashion in postnatal and adult mice. genesis 47:805–814, 2009. © 2009 Wiley‐Liss, Inc.