Humanized mouse models in transplantation research

Hogenes, Marieke C.H.; Huibers, Manon M. H.; Kroone, Chantal; Weger, Roel de

doi:10.1016/j.trre.2014.02.002

Cited by 20 publications

(33 citation statements)

References 78 publications

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“…Indeed, for more than 10 years, the NOD/ scid mouse was considered the “gold standard” for long-term repopulation of human hemato-lymphoid cells (25;26;55;68). Investigators found that the engraftment of human peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs) was 5–10-fold greater in NOD/ scid mice when compared to scid mice (25;52;55;69).…”

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

“…Because these cytokines are required for T, B and NK cell development, targeted mutation of IL-2rγ resulted in the loss of receptor-ligand signaling thereby creating mice devoid of T, B and NK cells (73–75). Over the next few years, several laboratories developed immunodeficient mice devoid of IL-2rγ that differed with respect to strain background and the type of IL-2rγ mutation (26;28;68) (Table 2). The nomenclature for describing and categorizing the different IL-2rγ−/− strains may appear a bit confusing for those readers who are not mouse geneticists.…”

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

“…These mice express a truncated/inactive form of IL-2rγ similar to that expressed in NOG mice. We refer readers to several recent reviews that describe the generation and unique characteristics of these different (26;28;68;69). …”

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

“…The development of these immuno-deficient IL-2rγ −/− strains was a defining moment in the quest to humanize the mouse immune system as each of these stocks were shown to engraft human hematopoietic stem cells (HSCs) or peripheral blood mononuclear cells (PBMCs) to a much greater extent than had been observed for any of the previous immuno-deficient strains (26;28;68;69). In addition, these new-generation IL-2rγ −/− mice do not develop thymic lymphomas and live a normal lifespan of 2 years.…”

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

“…Indeed, the generation of these immuno-deficient IL-2rγ −/− strains greatly advanced the field as investigators observed much greater levels of engraftment of T cells than had been documented in other lymphopenic recipients. In addition, lymphopenic IL-2rγ −/− strains possessed a much greater lifespan due to the lack of thymic lymphoma development (26;68;69). Intravenous injection of human PBMCs into irradiated (conditioned) or naive IL-2rγ −/− strains produces the most robust engraftment of human T cells than in any previous immuno-deficient recipient (79).…”

Section: Humanized Mouse Modelsmentioning

confidence: 99%

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Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases

Koboziev

Jones-Hall

Valentine

et al. 2015

Inflammatory Bowel Diseases

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Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases as well as assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically-effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient’s bedside, it is becoming increasingly apparent that the mouse immune system may not adequately recapitulate the immuno-pathological mechanisms observed in human diseases. Indeed, it is well-known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system in order to address important, human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hemato-lymphoid cells in mice would provide investigators with a relatively inexpensive, small animal model to study clinically-relevant mechanisms as well as facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic inflammatory diseases. In addition, we discuss current challenges and possible solutions for utilizing these unique mouse models to define the human-specific immuno-pathological mechanisms responsible for the induction and perpetuation of chronic gut inflammation.

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Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

Section: The Use Of Immuno-deficient Mice As Recipients For Human Hemmentioning

confidence: 99%

Section: Humanized Mouse Modelsmentioning

confidence: 99%

See 3 more Smart Citations

Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases

Koboziev

Jones-Hall

Valentine

et al. 2015

Inflammatory Bowel Diseases

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Mouse Models of Chronic Intestinal Inflammation: Characterization and Use in Pharmacological Intervention Studies

Webb

Grisham

2017

Crohn's Disease and Ulcerative Colitis

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Mouse Models of the Humanized Immune System

Jain

Sinha

Mohan

et al. 2021

Essentials of Laboratory Animal Science: Principles and Practices

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Humanized mouse models in transplantation research

Cited by 20 publications

References 78 publications

Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases

Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases

Mouse Models of Chronic Intestinal Inflammation: Characterization and Use in Pharmacological Intervention Studies

Mouse Models of the Humanized Immune System

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