• CCR2 is a chemokine receptor that binds to monocyte chemoattractant proteins (MCP-1, 2, 3, and 4). The adhesion of monocytes to the arterial endothelium and their subsequent migration into the intima are pivotal events in the pathogenesis of atherosclerosis. Both CCR2 and MCP-1 have been implicated in atherosclerotic plaques. Specifically, MCP-1 is induced by modified LDL in endothelial cells and may facilitate the firm adhesion of monocytes to the vascular endothelium under flow conditions.
• Gene editing strategy: The exon 3 of the mouse Ccr2 gene that encodes the whole molecule (ATG to STOP codon) was replaced by the part of human exon 2 to exon 3 in B-hCCR2 mice(C). The human CCR2 expression is driven by the mouse Ccr2 promoter, while the mouse Ccr2 gene transcription and translation will be disrupted.
• Validation: Mouse CCR2 was only detectable in wild-type BALB/cCrSlcNifdc mice. Human CCR2 was exclusively detectable in homozygous B-hCCR2 mice(C), but not in wild-type BALB/cCrSlcNifdc mice.
• Application: Applied to the efficacy evalsuation and toxicity assessment in the field of atherosclerosis.

Gene targeting strategy for B-hCCR2 mice(C). The exon 3 of the mouse Ccr2 gene that encodes the whole molecule (ATG to STOP codon) was replaced by the part of human exon 2 to exon 3 in B-hCCR2 mice(C). The human CCR2 expression is driven by the mouse Ccr2 promoter, while the mouse Ccr2 gene transcription and translation will be disrupted.

Strain specific CCR2 expression analysis in wild-type BALB/cCrSlcNifdc mice and homozygous humanized B-hCCR2 mice(C) by flow cytometry. Spleen were collected from wild-type BALB/cCrSlcNifdc mice (+/+) and homozygous B-hCCR2 mice(C) (H/H). Protein expression was analyzed with anti-mouse CCR2 antibody (Biolegend, 150627) and anti-human CCR2 antibody (Biolegend, 357205) by flow cytometry. Mouse CCR2 was only detectable in wild-type BALB/cCrSlcNifdc mice. Human CCR2 was exclusively detectable in homozygous B-hCCR2 mice(C), but not in wild-type BALB/cCrSlcNifdc mice.