B6-hCXCR2 Mice

Catalog Number: C001626

Strain Name: C57BL/6NCya-Cxcr2em1(hCXCR2)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

C-X-C motif chemokine receptor 2 (CXCR2), encoded by the CXCR2 gene, is a member of the G protein-coupled receptor family [1]. While predominantly expressed in neutrophils, CXCR2 is also found in diverse tissue cells, including brain, lung, and other immune cell types [1-2]. As a cell surface receptor, CXCR2 binds specific chemokines, such as interleukin-8 (IL-8) and CXCL1, initiating intracellular signaling cascades involving phosphatidylinositol-3 kinase (PI3K), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways [2]. The principal physiological role of CXCR2 is to mediate neutrophil chemotaxis to sites of inflammation, thereby contributing to immune responses and inflammatory processes [3]. Additionally, CXCR2 has been implicated in the development and progression of various cancers, including melanoma, pancreatic, ovarian, breast, and prostate cancers, by regulating tumor cell survival, proliferation, metastasis, and angiogenesis [1-4]. Aberrant CXCR2 expression or function is associated with a range of pathological conditions, encompassing both inflammatory diseases and cancers.

The B6-hCXCR2 mouse is a humanized model constructed using gene editing technology to replace the entire base sequence of the mouse Cxcr2 gene in situ with the corresponding sequence from the human CXCR2 gene. Homozygous B6-hCXCR2 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of inflammatory diseases and cancers, and for the development of CXCR2-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hCXCR2 mice. The sequence from ATG start codon to TAA stop codon of the endogenous mouse Cxcr2 gene was replaced with the sequence from ATG start codon to TAA stop codon of the human CXCR2 gene.

 

Application

  • CXCR2-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of inflammatory diseases and cancers.

 

References
[1]Korbecki J, Kupnicka P, Chlubek M, Gorący J, Gutowska I, Baranowska-Bosiacka I. CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer. Int J Mol Sci. 2022 Feb 16;23(4):2168.
[2]Lazennec G, Rajarathnam K, Richmond A. CXCR2 chemokine receptor - a master regulator in cancer and physiology. Trends Mol Med. 2024 Jan;30(1):37-55.
[3]Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, Clark W, Gilroy K, Hedley A, Nixon C, Luli S, Laszczewska M, Pinyol R, Esteban-Fabró R, Willoughby CE, Haber PK, Andreu-Oller C, Rahbari M, Fan C, Pfister D, Raman S, Wilson N, Müller M, Collins A, Geh D, Fuller A, McDonald D, Hulme G, Filby A, Cortes-Lavaud X, Mohamed NE, Ford CA, Raffo Iraolagoitia XL, McFarlane AJ, McCain MV, Ridgway RA, Roberts EW, Barry ST, Graham GJ, Heikenwälder M, Reeves HL, Llovet JM, Carlin LM, Bird TG, Sansom OJ, Mann DA. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut. 2022 Apr 27;71(10):2093–106.
[4]Cheng Y, Mo F, Li Q, Han X, Shi H, Chen S, Wei Y, Wei X. Targeting CXCR2 inhibits the progression of lung cancer and promotes therapeutic effect of cisplatin. Mol Cancer. 2021 Apr 4;20(1):62.