Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes

Abstract

Genetically engineered mouse models are commonly preferred for studying the human disease due to genetic and pathophysiological similarities between mice and humans. In particular, Cre-loxP system is widely used as an integral experimental tool for generating the conditional. This system has enabled researchers to investigate genes of interest in a tissue/cell (spatial control) and/or time (temporal control) specific manner. A various tissue-specific Cre-driver mouse lines have been generated to date, and new Cre lines are still being developed. This review provides a brief overview of Cre-loxP system and a few commonly used promoters for expression of tissue-specific Cre recombinase. Also, we finally introduce some available links to the Web sites that provides detailed information about Cre mouse lines including their characterization.

Loss of receptor tyrosine kinase-like orphan receptor 2 impairs the osteogenesis of mBMSCs by inhibiting signal transducer and activator of transcription 3

“…The Prrx1-Cre mice express Cre recombinase under the regulation of the paired related homeobox gene-1(Prx1)-derived regulatory element [19,20]. When Prrx1-Cre transgenic mice are crossed with a strain containing a loxp site-flanked sequence of interest, Cre-mediated recombination results in deletion of the floxed sequence in all mesenchyme-derived cells in the limbs and craniofacial tissue [19][20][21][22]. Therefore, in order to elucidate the role of Ror2 in osteogenesis of osteoblastic cell lineages in vivo, Ror2 f/f transgenic mice which possess loxp sites flanking exons 3-4 of Ror2 gene [23] and the Prrx1-Cre transgenic mice were used to generate mice with Ror2 gene-specific deletion in mesenchymal progenitors.…”

Generation of PECAM‐1 (CD31) conditional knockout mice

“…Mixed bone marrow chimera studies have also shown that endothelial PECAM‐1 is necessary but not sufficient to suppress atherosclerosis in some regions of the vasculature (Goel et al, ; Harrison et al, ). Breeding of PECAM1 flox/flox mice with endothelial cell‐ or hematopoietic cell‐specific (Kim, Kim, Im, & Fang, ) Cre recombinase‐expressing mice can be used to confirm this conclusion, and mice that express Cre recombinase in specific populations of immune cells (Kim et al, ) or platelets (Nagy et al, ; Tiedt, Schomber, Hao‐Shen, & Skoda, ) can be used to determine on which hematopoietic cells expression of PECAM‐1 is important for modulation of this disease. Breeding of PECAM1 flox/flox mice with mice in which Cre recombinase is expressed specifically in dendritic cells (Mattiuz et al, ; Salvermoser et al, ) can be used to determine the importance of dendritic cell expression of PECAM‐1 for control of experimental autoimmune encephalomyelitis, as has been previously proposed (Clement et al, ).…”

“…Breeding of PECAM1 flox/flox mice with mice in which Cre recombinase is expressed specifically in dendritic cells (Mattiuz et al, ; Salvermoser et al, ) can be used to determine the importance of dendritic cell expression of PECAM‐1 for control of experimental autoimmune encephalomyelitis, as has been previously proposed (Clement et al, ). Similarly, breeding PECAM1 flox/flox mice with mice that express Cre recombinase in CD4 + T cells (Kim et al, ) can help to verify their postulated role in resistance to bacterial infection (Ross et al, ). Finally, PECAM1 flox/flox and tissue‐specific Cre recombinase‐expressing mice can be used to identify the specific PECAM‐1‐expressing cells that control inflammatory diseases of the liver (Goel et al, ; G. Malik et al, ; I.…”

“…Mixed bone marrow chimera studies have also shown that endothelial PECAM-1 is necessary but not sufficient to suppress atherosclerosis in some regions of the vasculature (Goel et al, 2008;Harrison et al, 2013). Breeding of PECAM1 flox/flox mice with endothelial cell-or hematopoietic cellspecific (Kim, Kim, Im, & Fang, 2018) Cre recombinase-expressing mice can be used to confirm this conclusion, and mice that express Cre recombinase in specific populations of immune cells (Kim et al, 2018) or platelets (Nagy et al, 2019; Tiedt, Schomber, Hao-Shen, & F I G U R E 6 Platelets isolated from Sox2Cre;PECAM1 del/del mice are hyper-responsive to stimulation via the GPVI/FcRγ collagen receptor than are those isolated from PECAM1 flox/flox mice. Washed platelets prepared from PECAM1 flox/flox (black) and Sox2Cre;PECAM1 del/del (red) mice were stimulated with a low (left) or high (right) dose of collagen-related peptide (CRP).…”

Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology

“…To overcome these obstacles, conditional gene knockout with the Cre-loxP recombination system [31] Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s1103 3-019-05214 -7) contains supplementary material, which is available to authorized users. is widely used to eliminate a specific gene in a particular tissue at a certain development stage [15]. Many mouse stem cell clones have been developed by the International Knockout Mouse Consortium with putative conditional null mutations that are being used to generate conditional mice [1,8].…”