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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Fayez M SalehUssama M Abdel-Motal

Abstract

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 α1,3 galactosyltransferase (α1,3GT) gene and lack α-Gal epitopes on glycosylated proteins, whereas mice and other nonprimate mammals express this epitope. The lack of α-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 α-Gal epitopes because they express α-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 α-Gal epitopes and secretes human anti-Gal Abs. The new humanized mouse model (Hu-NSG/α-Galnull) is designed to be used for preclinical evaluations of viral and tumor vaccines based on α-Gal epitopes, human-...Continue Reading

References

Jul 1, 1990·Immunology Today·H G Ljunggren, K Kärre
Oct 1, 1994·Immunological Reviews·M S Sandrin, I F McKenzie
Mar 8, 2000·The Journal of Experimental Medicine·M K KennedyJ J Peschon
Jan 5, 2002·The Journal of Biological Chemistry·Chihiro KoikeMassimo Trucco
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danita H SchuurhuisFerry Ossendorp
Mar 5, 2002·Nature Biotechnology·Yifan DaiDavid L Ayares
Dec 21, 2002·Science·Carol J PhelpsDavid L Ayares
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leonard D ShultzRupert Handgretinger
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Uri GaliliUssama M Abdel-Motal
Oct 13, 2012·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Apr 5, 2013·Xenotransplantation·Kyoung-Soon JangByung-Gee Kim
Nov 14, 2015·AIDS Research and Human Retroviruses·Kang Chang KimYoung Bong Kim

❮ Previous
Next ❯

Citations

Jul 28, 2021·PLoS Neglected Tropical Diseases·Gisele Macêdo Rodrigues da CunhaAlexandre Ferreira Marques

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.