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Publication : A New Humanized Mouse Model Mimics Humans in Lacking α-Gal Epitopes and Secreting Anti-Gal Antibodies.

First Author  Saleh FM Year  2020
Journal  J Immunol Volume  204
Issue  7 Pages  1998-2005
PubMed ID  32144163 Mgi Jnum  J:287591
Mgi Id  MGI:6406028 Doi  10.4049/jimmunol.1901385
Citation  Saleh FM, et al. (2020) A New Humanized Mouse Model Mimics Humans in Lacking alpha-Gal Epitopes and Secreting Anti-Gal Antibodies. J Immunol 204(7):1998-2005
abstractText  Mice have been used as accepted tools for investigating complex human diseases and new drug therapies because of their shared genetics and anatomical characteristics with humans. However, the tissues in mice are different from humans in that human cells have a natural mutation in the alpha1,3 galactosyltransferase (alpha1,3GT) gene and lack alpha-Gal epitopes on glycosylated proteins, whereas mice and other nonprimate mammals express this epitope. The lack of alpha-Gal epitopes in humans results in the loss of immune tolerance to this epitope and production of abundant natural anti-Gal Abs. These natural anti-Gal Abs can be used as an adjuvant to enhance processing of vaccine epitopes to APCs. However, wild-type mice and all existing humanized mouse models cannot be used to test the efficacy of vaccines expressing alpha-Gal epitopes because they express alpha-Gal epitopes and lack anti-Gal Abs. Therefore, in an effort to bridge the gap between the mouse models and humans, we developed a new humanized mouse model that mimics humans in that it lacks alpha-Gal epitopes and secretes human anti-Gal Abs. The new humanized mouse model (Hu-NSG/alpha-Gal(null)) is designed to be used for preclinical evaluations of viral and tumor vaccines based on alpha-Gal epitopes, human-specific immune responses, xenotransplantation studies, and in vivo biomaterials evaluation. To our knowledge, our new Hu-NSG/alpha-Gal(null) is the first available humanized mouse model with such features.
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