Basic Information

Strain Name
C57BL/6-Ccr8tm1(CCR8)/Bcgen
Stock Number
110096
Common Name
B-hCCR8 mice
Background
C57BL/6
Aliases
C-C motif chemokine receptor 8; CY6; TER1; CCR-8; CKRL1; CDw198; CMKBR8; GPRCY6; CMKBRL2; CC-CKR-8
Targeting Strategy
Exon 2 (which encodes the full length coding sequence) of mouse Ccr8 was replaced by human CCR8 exon 2 in B-hCCR8 mice.
NCBI Gene ID

Details

mRNA expression analysis

CCR8 gene expression in C57BL/6 and B-hCCR8 mice by RT-PCR. Mouse Ccr8 mRNA was detectable in thymocytes of wild-type mice (+/+) . Human CCR8 mRNA was detectable only in homozygous B-hCCR8 mice (H/H) but not in wild-type mice (+/+).

Protein expression analysis

Human CCR8 expression in B-hCCR8 mice. MC38 tumor cells were inoculated into wild-type C57BL/6 (+/+) and homozygous B-hCCR8 mice (H/H). Tumors were harvested at the endpoint of experiment, and tumor-infiltrating lymphocytes were analyzed by flow cytometry. Human CCR8 was detected on CD4+ T cells and Treg cells in tumors from homozygous B-hCCR8 mice, while mouse CCR8 was detected only in wild-type mice.

Tissue distribution of CCR8+ T lymphocytes in wildtype and B-hCCR8 mice bearing tumors. Human CCR8 was detected on CD4+ T cells and Treg cells in tumors isolated from homozygous B-hCCR8 mice, but not those T cells isolated from spleen or blood. Similarly, mouse CCR8 was detected in tumors and expressed on some T cells isolated from wild-type mice, but not on blood cells.

In vivo efficacy

Antitumor activity of anti-human CCR8 antibody in male B-hCCR8 mice

(A) Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCCR8 mice (male, 6-7 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human CCR8 antibodies as indicated. (B) Body weight changes during treatment. As shown in panel A, anti-human CCR8 antibodies blunted tumor growth. Values are expressed as mean ± SEM.

Antitumor activity of anti-human CCR8 antibody in female B-hCCR8 mice

(A) Anti-human CCR8 antibody inhibited MC38 tumor growth in B-hCCR8 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCCR8 mice (female, 8 week-old, n=8). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human CCR8 antibody as indicated. (B) Body weight changes during treatment. As shown in panel A, anti-human CCR8 antibody blunted tumor growth in B-hCCR8 mice.  Values are expressed as mean ± SEM.