B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice

Basic Information

Common Name
B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice
Background
C57BL/6
Catalog Number
112846
NCBI Gene ID
16189, 16190, 53603, 57914
Aliases
BCGF-1, BCGF1, BSF-1, BSF1, IL-4; CD124, IL-4RAA, IL4R; CRL2Y, TSLPR, CRLF2

Targeting strategy

Gene targeting strategy for B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice. The exons 1-5 of mouse Tslp gene that encode the full-length protein were replaced by human TSLP exons 1-4 in B-hTSLP/hTSLPR mice plus. The signal peptide, extracellular and transmembrane region of human TSLPR gene and the cytoplasmic region of mouse Tslpr gene were constructed into a chimeric CDS vector and inserted into the mouse exon 2.The targeted mice will express the chimeric TSLPR protein, while mouse TSLPR will no longer express in B-hTSLP/hTSLPR mice plus. The exons 1-4 of mouse Il4 gene that encode the full length coding sequence were replaced by human IL4 exons 1-4 in B-hIL4/hIL4RA mice. The exons 4-7 of mouse Il4ra gene that encode the extracellular region coding sequences were replaced by human IL4RA exons 4-7 in B-hIL4/hIL4RA mice. B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice was developed by cross-mating the B-hTSLP/hTSLPR mice plus and the B-hIL4/hIL4RA mice together.

In vivo efficacy of anti-TSLP and IL-4 related antibody in a new mouse asthma model

Analysis of immune cells in BALF by flow cytometry. B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice (female, 7-week-old, n=6) were immunized with OVA and TSLP to induce asthma. TSLP-related antibody, IL4-related antibody or bispecific antibody (BsAb) (TSLP-related antibody, IL4-related antibody or BsAb provided by client) were intraperitoneally injected in G3-G5. Broncheoalveolar fluid (BALF) was collected at the end of the experiment to detect inflammatory cell infiltration in lung tissue. The results showed that the proportion of eosinophils induced in the treated OVA/TSLP group (G2) was significantly higher than that in the uninduced group (G1), while the proportion of these cells in the treated group (G3-G5) decreased significantly when compared with the TSLP/OVA-induced isotype treated group. Data indicated that TSLP-related antibody, IL4-related antibody or BsAb could effectively reduce the number and proportion of eosinophils in B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice induced with TSLP/OVA. Values are expressed as mean ± SEM. Significance was determined by one-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001. The overage of this mouse model is 20%.

Total IgE in serum was reduced in the mouse asthma model treated with TSLP-related antibody, IL4-related antibody or BsAb. Serum was collected at the study endpoint. IgE levels were analyzed by ELISA. The results showed that the levels of total IgE in mice treated with TSLP-related antibody, IL4-related antibody or BsAb were lower than that in untreated mice. Values are expressed as mean ± SEM. Significance was determined by one-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.

H&E staining of asthma-like model in B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice. Lung tissues were collected at the study endpoint and analyzed with H&E staining. The results showed that compared to the untreated group (G2), the groups of mice treated with TSLP-related antibody, IL4-related antibody or BsAb showed a significant reduction in inflammatory infiltration in lung tissue, indicating that B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice provide a powerful preclinical model for in vivo evaluation of TSLP-related antibody, IL4-related antibody or BsAb. Values are expressed as mean ± SEM. Significance was determined by one-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.

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