Basic Information

Strain Name
C57BL/6-Klrd1tm1(KLRD1)Klrc1tm1(KLRC1)/Bcgen
Stock Number
121077
Common Name
B-hCD94/hNKG2A mice
Background
C57BL/6
Related Genes
CD94,KLRD1, NKG2A, KLRC1, CD159a
NCBI Gene ID

Targeting Strategy

Exons 3~6 of mouse the Klrd1 gene (which encode the extracellular domain) were replaced by human KLRD1 exons 3~6 in B-hCD94 mice. Exons 2~6 of the mouse Klrc1 gene (which encode the extracellular domain) were replaced by human KLRC1 exons 2~6 in B-hNKG2A mice.

mRNA Expression

Strain specific analysis of CD94 and NKG2A gene expression in WT and homozygous B-hCD94/hNKG2A mice by RT-PCR. Mouse Cd94 and Nkg2a mRNA were detectable in splenocytes of wild-type (+/+) mice. Human CD94 and NKG2A mRNA were detectable only in the homozygous B-hCD94/hNKG2A, but not in +/+ mice.

Protein Expression Details

Protein expression analysis in NK cells

Strain specific CD94 and NKG2A expression analysis in homozygous B-hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCD94/hNKG2A (H/H) mice, and analyzed by flow cytometry with species-specific CD94 or NKG2A antibody. Mouse CD94 and NKG2A were detectable in WT mice. Human CD94 and NKG2A were exclusively detectable in homozygous B-hCD94/hNKG2A but not WT mice. (Monalizumab was  used to detect the human NKG2A protein in WT and homozygous B-hCD94/hNKG2A)

In Vivo Efficacy

In vivo efficacy of anti-human NKG2A antibody

Antitumor activity of anti-human NKG2A antibody in B-hCD94/hNKG2A mice. (A) Anti-human NKG2A antibody inhibited hHLA-E MC38 tumor growth in B-hCD94/hNKG2A mice. Murine colon cancer hHLA-E MC38 cells were subcutaneously implanted into homozygous B-hCD94/hNKG2A mice (female, 6-7 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, and treated with anti-hNKG2A antibody at doses and schedules in panel A. (B) Body weight changes during treatment. As shown in panel A, anti-human NKG2A antibody (monalizumab, in house) were efficacious in controlling tumor growth in B-hCD94/hNKG2A mice, demonstrating they provide a powerful preclinical model for in vivo evaluation of anti-human NKG2A antibody. Values are expressed as mean ± SEM.