4.7 Review

Humanized mouse models of genetic immune disorders and hematological malignancies

Journal

BIOCHEMICAL PHARMACOLOGY
Volume 174, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.113671

Keywords

Immune; Humanized; Mouse; Monogenic; Immunotherapy

Funding

  1. National Institute of Diabetes and Digestive and Kidney Diseases [DK106311]
  2. Academy Ter Meulen Grant from the Royal Netherlands Academy of Arts and Sciences
  3. Cultural Foundation Grant from Prince Bernhard Cultural Foundation
  4. joint Israel-US Binational Science Foundation (BSF) grant

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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.

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