Shultz, L.D. , Ishikawa, F. & Greiner, D.L. Humanized mice in translational biomedical research. Nat. Rev. Immunol. 7, 118-130

The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 03/2007; 7(2):118-30. DOI: 10.1038/nri2017
Source: PubMed


The culmination of decades of research on humanized mice is leading to advances in our understanding of human haematopoiesis, innate and adaptive immunity, autoimmunity, infectious diseases, cancer biology and regenerative medicine. In this Review, we discuss the development of these new generations of humanized mice, how they will facilitate translational research in several biomedical disciplines and approaches to overcome the remaining limitations of these models.

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    • "With an intact immune system these mice serve as a robust model of autoimmunity mediated type1 diabetes (Kolb, 1987). On an immune deficient background, however, they are the gold standard for human hematopoietic chimerism (Shultz et al., 2007). The NOD/SCID/interleukin receptor common γ-chain (Il2rg) knockout (NSG) mouse is used by many laboratories (Ito et al., 2002). "

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    • "" Humanized mice " refer to immature immunodeficient mice that are injected with human blood stem cells. As they mature, these mice develop a functional human immune system (Shultz et al., 2007, 2012). While many models and background strains have been used for this purpose, the NOD-SCID-IL2rg null (NSG) mouse is particularly effective at engrafting human blood stem cells and developing a wide range of functional human immune cell lineages (Coughlan et al., 2012; Brehm et al., 2010; Giassi et al., 2008; Ishikawa et al., 2005; Rajesh et al., 2010; Shultz et al., 2005; Tanaka et al., 2012). "
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    ABSTRACT: Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rg(null) (NSG) mice engrafted with human CD34(+) hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI should consider using the humanized mouse model. Humanized mice represent a powerful tool for improving the translational value of pre-clinical SCI data. Copyright © 2015. Published by Elsevier Inc.
    Experimental Neurology 07/2015; 271. DOI:10.1016/j.expneurol.2015.07.011 · 4.70 Impact Factor
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    • "However, as the immune systems of mice and humans are not identical, new research tools must be designed to aid in future studies. The development of humanized mice (Shultz et al., 2007) with immune cells of human origin may offer a possible research direction to define immunopathogenesis. The dream of having a chikungunya vaccine could be near with the success of the VLP vaccine (Chang et al., 2014). "
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    ABSTRACT: Chikungunya virus (CHIKV) is an arthropod-borne virus that causes chikungunya fever, a disease characterized by the onset of fever and rashes, with arthralgia as its hallmark symptom. CHIKV has re-emerged over the past decade, causing numerous outbreaks around the world. Since late 2013, CHIKV has reached the shores of the Americas, causing more than a million cases of infection. Despite concentrated efforts to understand the pathogenesis of the disease, further outbreaks remain a threat. This review highlights important findings regarding CHIKV-associated immunopathogenesis and offers important insights into future directions. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World." Copyright © 2015. Published by Elsevier B.V.
    Antiviral research 06/2015; 120. DOI:10.1016/j.antiviral.2015.06.009 · 3.94 Impact Factor
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