Humanized mouse models of genetic immune disorders and hematological malignancies

• Published in: Biochemical pharmacology 2020-04, Vol.174, p.113671-113671, Article 113671
• Main Authors: Tyagi, Rajeev K., Li, Jing, Jacobse, Justin, Snapper, Scott B., Shouval, Dror S., Goettel, Jeremy A.
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Gene Editing; Hematologic Neoplasms - genetics; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Humanized; Humans; Immune; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Immunologic Deficiency Syndromes - therapy; Immunotherapy; Mice; Mice, Inbred NOD; Mice, SCID; Monogenic; Mouse
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2019.113671

[Display omitted] The immune system is quite remarkable having both the ability to tolerate innocuous and self-antigens while possessing a robust capacity to recognize and eradicate infectious pathogens and foreign entities. The genetics that encode this delicate balancing act include multiple genes and specialized cell types. Over the past several years, whole exome and whole genome sequencing has uncovered the genetics driving many human immune-mediated diseases including monogenic disorders and hematological malignancies. With the advent of genome editing technologies, the ability to correct genetic immune defects in autologous cells holds great promise for a number of conditions. Since assessment of novel therapeutic strategies have been difficult in mice, in recent years, immunodeficient mice capable of engrafting human cells and tissue have been developed and utilized for a variety of research applications. In this review, we discuss immune-humanized mice as a research tool to study human immunobiology and genetic immune disorders in vivo and the promise of future applications.