Basic Information

Strain Name
C57BL/6-Cxcr4tm1(CXCR4)/Bcgen
Stock Number
110100
Common Name
B-hCXCR4 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
CXC-R4, CXCR-4, CD184

Description

C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. CXCR4’s ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. It has been also shown that CXCR4 signaling regulates the expression of CD20 on B cells. Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4. MIF is an additional ligand of CXCR4. Drugs that block the CXCR4 receptor appear to be capable of “mobilizing” hematopoietic stem cells into the bloodstream as peripheral blood stem cells. CXCR4 is mainly expressed on T, B, DC, NK, monocytes, while CXCR4’s expression is low or absent in many healthy tissues, it was demonstrated to be expressed in over 23 types of cancer, including breast cancer, ovarian cancer, melanoma, and prostate cancer. Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow. However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 expression is positively correlated with disease free (metastasis free) survival.

Targeting strategy

Gene targeting strategy for B-hCXCR4 mice. The exons 1~2 of mouse Cxcr4 gene that encode the full-length protein were replaced by human CXCR4 exons 1~2 in B-hCXCR4 mice.

mRNA expression analysis

Strain specific analysis of CXCR4 gene expression in WT and B-hCXCR4 mice by RT-PCR. Mouse Cxcr4 mRNA was detectable in splenocytes and thymocytes of wild-type (+/+). Human CXCR4 mRNA was detectable only in H/H, but not in +/+ mice.

 

Protein expression analysis in T cells

Strain specific CXCR4 expression analysis in homozygous B-hCXCR4 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCXCR4 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific CXCR4 antibody. Mouse CXCR4 was detectable in WT mice. Human CXCR4 was exclusively detectable in homozygous B-hCXCR4, but the expression level was significantly lower than mouse CXCR4 in the C57BL/6 mice.

Protein expression analysis in CD4+ T cells

Strain specific CXCR4 expression analysis in homozygous B-hCXCR4 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCXCR4 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific CXCR4 antibody. Mouse CXCR4 was detectable in WT mice. Human CXCR4 was exclusively detectable in homozygous B-hCXCR4, but the expression level was significantly lower than mouse CXCR4 in the C57BL/6 mice.

Protein expression analysis in B cells

Strain specific CXCR4 expression analysis in homozygous B-hCXCR4 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCXCR4 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific CXCR4 antibody. Mouse CXCR4 was detectable in WT mice. Human CXCR4 was exclusively detectable in homozygous B-hCXCR4, but the expression level was significantly lower than mouse CXCR4 in the C57BL/6 mice.