Basic Information

Strain Name
C57BL/6-Pdcd1tm1(PDCD1) Cd274tm1(CD274)/Bcgen
Stock Number
120522
Common Name
B-hPD-1/hPD-L1 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
PDCD1 (Programmed death-1, as known as PD-1); CD274 (Programmed cell death ligand-1, also known as B7-H1, PD-L1)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous
NCBI Gene ID

Gene targeting strategy

Gene targeting strategy for B-hPD-1/hPD-L1 mice. The exon 2 of mouse PD-1 gene that encodes the IgV domain was replaced by human PD-1 exon 2 in B-hPD-1/hPD-L1 mice. The exon 3 of mouse Pdl1 gene that encodes the IgV domain was replaced by human PD-L1 exon 3 in B-hPD-1/hPD-L1 mice. This double knock-in model, was developed by breeding the B-hPD-1 mice and the B-hPD-L1 mice.

mRNA expression analysis

Species-specific PD-1 and PD-L1 gene expression analysis in wild-type and humanized B-hPD-1/hPD-L1 mice by RT-PCR. Mouse Pd-1 and PD-L1 mRNAs were detected in splenocytes isolated from wild-type C57BL/6 (+/+) mice, while human PD-1 and PD-L1 mRNAs were detected in homozygous B-hPD-1/hPD-L1 (H/H) mice.

Protein expression analysis

Species-specific PD1 and PD-L1 protein expression analysis in wild-type and humanized B-hPD-1/hPD-L1 mice. Splenocytes were isolated from wild-type C57BL/6 (+/+) and homozygous B-hPD-1/hPD-L1 mice (H/H) stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry using species-specific anti-PD-1 and anti-PD-L1 antibodies. Mouse PD-1 and PD-L1 proteins were detected in wild-type mice, while human PD-1 and PD-L1 proteins were detected in B-hPD-1/hPD-L1 mice.

Blood chemistry

Blood routine test of B-hPD-1/hPD-L1 mice

Complete blood count (CBC)

Blood from female C57BL/6 and B-hPD-1/hPD-L1 mice (n = 5, 6 weeks-old) was collected and analyzed by CBC. There was no differences among any measurement between C57BL/6 and B-hPD-1/hPD-L1 mice.

Blood chemistry of B-hPD-1/hPD-L1 mice

Blood chemistry tests of B-hPD-1/hPD-L1 mice. Serum from the C57BL/6 and B-hPD-1/hPD-L1 mice (n = 3, 6 week-old) was collected and analyzed for levels of biochemistry. There was no differences on AST, ALB, GLU, CHOL, CREA measurement between C57BL/6 and B-hPD-1/hPD-L1,. ALT, TRIG, UREA have significant changes compared to wild-type mice. Values are expressed as mean ± SEM.

Blood chemistry tests of B-hPD-1/hPD-L1 mice. Serum from the C57BL/6 and B-hPD-1/hPD-L1 mice (n = 3, 6 week-old) was collected and analyzed for levels of biochemistry. There was no differences on AST, ALB, GLU, CHOL, CREA measurement between C57BL/6 and B-hPD-1/hPD-L1. Values are expressed as mean ± SEM.

In vivo efficacy

In vivo efficacy of anti-human PD-1 antibody

Antitumor activity of anti-human PD-1 antibody in B-hPD-1/hPD-L1 mice. (A) Anti-human PD-L1 antibody Pembrolizumab (in house) inhibited B-hPD-L1 MC38 plus tumor growth in B-hPD-1/hPD-L1 mice. Murine colon cancer B-hPD-L1 MC38 plus cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hPD-L1 mice (male, 8-week-old, n=5). Mice were grouped when tumor volume reached approximately 80mm3, at which time they were treated with anti-human PD-1 antibody with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, different doses of human PD-1 antibody inhibited tumor growth in different levels, demonstrating that the B-hPD-1/hPD-L1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

In vivo efficacy of anti-human PD-L1 antibody

Antitumor activity of anti-human PD-L1 antibody in B-hPD-1/hPD-L1 mice. (A) Anti-human PD-L1 antibody atezolizumab (in house) inhibited B-hPD-L1 MC38 plus tumor growth in B-hPD-1/hPD-L1 mice. Murine colon cancer B-hPD-L1 MC38 plus cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hPD-L1 mice (male, 5-week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-L1 antibody with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, different doses of human PD-L1 antibody inhibited tumor growth in different levels, demonstrating that the B-hPD-1/hPD-L1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-L1 antibodies. Values are expressed as mean ± SEM.

Publications using B-hPD-1/hPD-L1 mice

  1. Park JJ, Thi EP, Carpio VH, Bi Y, Cole AG, Dorsey BD, Fan K, Harasym T, Iott CL, Kadhim S, Kim JH, Lee ACH, Nguyen D, Paratala BS, Qiu R, White A, Lakshminarasimhan D, Leo C, Suto RK, Rijnbrand R, Tang S, Sofia MJ, Moore CB. Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1. Nat Commun. 2021 Feb 22;12(1):1222. doi: 10.1038/s41467-021-21410-1. PMID: 33619272.

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