Great tool for investigating human IgE inhibition - Human IgE (ε, κ) Knock-In mice
2023-02-20
The importance of IgE in mediating allergic responses and parasitic worm infestations
One of the five immunoglobulin classes, immunoglobulin E (IgE), is identified by the presence of the epsilon (ε) heavy chain. It is found in the bloodstream in very small amounts, around 300 times lower than IgG. Despite being the least abundant, it is in many ways the most influential one among the antibodies found in mammals. In serum, it has a half-life of 2-3 days. In order to protect against allergic responses and parasitic worm infestations, IgE is produced by IgE plasma cells, which are found in mucosal tissues, particularly in the respiratory tract and the gastrointestinal tract.
IgE plays a central role in mediating type I hypersensitivity reactions that are responsible for causing allergic diseases, including allergic asthma, allergic rhinitis, atopic dermatitis, and others.
What’s the IgE mouse model?
In the past, researchers would use the PBMC collected from allergic patients to do the IgE inhibition experiments. Croyez offers a great new option for our customers which is the Human IgE (ε, κ) knock-in mice (HεκKI mice). This is a mouse model, in whose genome the Cγ1 constant regions are replaced by the human immunoglobulin Cε constant regions, and the Cκ constant region is replaced by the human immunoglobulin Cκ constant region.
The HεκKI mice produce humanized IgE-secreting B cells and humanized IgE that is specific to an antigen after immunization and are employed to perform chimeric human IgE inhibition by antibodies, small molecules, or vaccines.
Features
- 30-fold higher human IgE response than mouse IgE
- Not produce mouse IgG1
Serum levels of immunoglobulins of different isotypes in the three genotypes of mice that were immunized on day 1 and day 29. The data shows HεκKI mice were with a higher level of hIgE and similar levels of other IgG isotypes. [1]
Application
- Contract research or drug development
- Chimeric human IgE inhibition animal model
The customer who worked on chronic spontaneous urticaria (CSU) drug development utilized the hIgE transgenic mice model to comprehend the level of serum free-chimeric-IgE. [2]
In these mice (N=6), UB-221 can significantly lower the elevated serum free-chimeric-IgE level by more than 90% after a single intraperitoneal injection of 0.3 mg/ kg (Figure. A) or 3.0 mg/ kg (Figure. B).
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Please feel free to contact us if you are interested in this animal model. We are happy to share more information with you.
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Lu CS, Hung AF, Lin CJ, Chen JB, Chen C, Shiung YY, Tsai CY, Chang TW. Generating allergen-specific human IgEs for immunoassays by employing human ε gene knockin mice. Allergy. 2015 Apr;70(4):384-90.
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Kuo BS, Li CH, Chen JB, Shiung YY, Chu CY, Lee CH, Liu YJ, Kuo JH, Hsu C, Su HW, Li YF, Lai A, Ho YF, Cheng YN, Huang HX, Lung MC, Wu MS, Yang FH, Lin CH, Tseng W, Yang J, Lin CY, Tsai PH, Chang HK, Wang YJ, Chen T, Lynn S, Liao MJ, Wang CY. IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms. J Clin Invest. 2022 Aug 1;132(15):e157765.