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B-hPD-1/hPD-L1/h4-1BB mice​
Strain Name C57BL/6-Pdcd1tm1(PDCD1) Cd274tm1(CD274)Tnfrsf9tm1(TNFRSF9)/Bcgen Common Name  B-hPD-1/hPD-L1/h4-1BB mice
Background C57BL/6 Catalog number  130569
Related Genes 

PD-1(Programmed death-1) 

NFRSF9(TNF receptor superfamily member 9, also known as 4-1BB)

NCBI Gene ID
18566,60533,21942

Targeting strategy


Gene targeting strategy for B-hPD-1/hPD-L1/h4-1BB mice. 

The exon 2 of mouse PD-1 gene that encode the IgV domain were replaced by human PD-1 exon 2 in B-hPD-1/hPD-L1/h4-1BB mice. The exon 3 of mouse Pd-l1 gene that encode the IgV domain were replaced by human PD-L1 exon 3 in B-hPD-L1/hPD-L1/h4-1BB mice. The exons 2-7 of mouse 4-1bb gene that encode the extracellular domain were replaced by human 4-1BB exons 2-7 in B-hPD-1/hPD-L1/h4-1BBmice.


Protein expression analysis


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Strain specific PD-1 expression analysis in homozygous B-hPD-1/hPD-L1/h4-1BB mice by flow cytometry. 

Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-hPD-1, anti-PD-L1 and anti-4-1BB antibody. Mouse PD-1, PD-L1 and 4-1BB were detectable in WT mice but not in homozygous B-hPD-1/hPD-L1/h4-1BB mice. Human PD-1, PD-L1 and 4-1BB were exclusively detectable in homozygous B-hPD-1/hPD-L1/h4-1BB mice but not WT mice.


Combination therapy of anti-human PD-L1 antibody and anti-human 4-1BB antibody


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Antitumor activity of anti-human PD-L1 antibody combined with anti-human 4-1BB antibody in B-hPD-1/hPD-L1/h4-1BB mice. 

(A) Anti-human PD-L1 antibody (in house) combined with anti-human 4-1BB antibody (in house) inhibited MC38 tumor growth in B-hPD-1/hPD-L1/h4-1BB mice. Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1/hPD-L1/h4-1BB mice (female, 6-7 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with human PD-L1 and human 4-1BB antibodies in panel A. (B) Body weight changes during treatment. Values are expressed as mean ± SEM.