scholarly journals Humanized mice

2005 ◽  
Vol 202 (10) ◽  
pp. 1307-1311 ◽  
Author(s):  
Francesca Macchiarini ◽  
Markus G. Manz ◽  
A. Karolina Palucka ◽  
Leonard D. Shultz
Keyword(s):  
Genetic Diversity ◽  
Human Physiology ◽  
Animal Models ◽  
Infectious Diseases ◽  
Mouse Models ◽  
Humanized Mice ◽  
Humanized Mouse ◽  
Humanized Mouse Models ◽  
The Creation ◽  
Physiological Systems

Animal models have been instrumental in increasing the understanding of human physiology, particularly immunity. However, these animal models have been limited by practical considerations and genetic diversity. The creation of humanized mice that carry partial or complete human physiological systems may help overcome these obstacles. The National Institute of Allergy and Infectious Diseases convened a workshop on humanized mouse models for immunity in Bethesda, MD, on June 13–14, 2005, during which researchers discussed the benefits and limitations of existing animal models and offered insights into the development of future humanized mouse models.

scholarly journals Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 776
Author(s):  
Kazutaka Terahara ◽  
Ryutaro Iwabuchi ◽  
Yasuko Tsunetsugu-Yokota
Keyword(s):  
Mouse Models ◽  
Humanized Mice ◽  
Lymphoid Tissues ◽  
Humanized Mouse ◽  
Hiv Pathogenesis ◽  
Hematopoietic Stem ◽  
Critical Issues ◽  
In Vivo Animal Models ◽  
Humanized Mouse Models

A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. These limitations are common in many humanized mouse models and are critical issues that need to be addressed. As distinct defects exist in each model, we need to be cautious about the experimental design and interpretation of the outcomes obtained using humanized mice. Considering this point, we mainly characterize the current conventional humanized mouse reconstituted only with HSCs and describe past achievements in this area, as well as the potential contributions of the humanized mouse models for the study of HIV pathogenesis and therapy. We also discuss the use of various technologies to solve the current problems. Humanized mice will contribute not only to the pre-clinical evaluation of anti-HIV regimens, but also to a deeper understanding of basic aspects of HIV biology.

scholarly journals Generation of improved humanized mouse models for human infectious diseases

2014 ◽  
Vol 410 ◽  
pp. 3-17 ◽  
Author(s):  
Michael A. Brehm ◽  
Michael V. Wiles ◽  
Dale L. Greiner ◽  
Leonard D. Shultz
Keyword(s):  
Infectious Diseases ◽  
Mouse Models ◽  
Humanized Mouse ◽  
Humanized Mouse Models

scholarly journals Modelling of human herpesvirus infections in humanized mice

2014 ◽  
Vol 95 (10) ◽  
pp. 2106-2117 ◽  
Author(s):  
Bradford K. Berges ◽  
Anne Tanner
Keyword(s):  
Mouse Models ◽  
Immune Cells ◽  
Human Herpesvirus ◽  
Antiviral Drugs ◽  
Humanized Mice ◽  
Great Promise ◽  
Humanized Mouse ◽  
Herpes Simplex Viruses ◽  
Human Immune ◽  
Humanized Mouse Models

The human herpesviruses (HHVs) are remarkably successful human pathogens, with some members of the family successfully establishing infection in the vast majority of humans worldwide. Although many HHV infections result in asymptomatic infection or mild disease, there are rare cases of severe disease and death found with nearly every HHV. Many of the pathogenic mechanisms of these viruses are poorly understood, and in many cases, effective antiviral drugs are lacking. Only a single vaccine exists for the HHVs and researchers have been unable to develop treatments to cure the persistent infections associated with HHVs. A major hindrance to HHV research has been the lack of suitable animal models, with the notable exception of the herpes simplex viruses. One promising area for HHV research is the use of humanized mouse models, in which human cells or tissues are transplanted into immunodeficient mice. Current humanized mouse models mostly transplant human haematopoietic stem cells (HSCs), resulting in the production of a variety of human immune cells. Although all HHVs are thought to infect human immune cells, the beta- and gammaherpesviruses extensively infect and establish latency in these cells. Thus, mice humanized with HSCs hold great promise to study these herpesviruses. In this review, we provide a historical perspective on the use of both older and newer humanized mouse models to study HHV infections. The focus is on current developments in using humanized mice to study mechanisms of HHV-induced pathogenesis, human immune responses to HHVs and effectiveness of antiviral drugs.

Humanized mouse models of infectious diseases

2012 ◽  
Vol 9 (1) ◽  
pp. e11-e16 ◽  
Author(s):  
Till Strowig ◽  
Richard A. Flavell
Keyword(s):  
Infectious Diseases ◽  
Mouse Models ◽  
Humanized Mouse ◽  
Humanized Mouse Models

scholarly journals Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1847
Author(s):  
Sushmita Negi ◽  
Sheetal Saini ◽  
Nikunj Tandel ◽  
Kiran Sahu ◽  
Ravi P.N. Mishra ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
T Cells ◽  
Mouse Models ◽  
Bowel Disease ◽  
Humanized Mice ◽  
Humanized Mouse ◽  
Inflammatory Bowel ◽  
Humanized Mouse Models

Crohn’s disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response. Phenotypic and functional characterization of various immune-suppressive T cells (regulatory T cells; Tregs) over the last decade has been used to optimize the procedures for in vitro expansion of these cells for developing therapeutic interventional strategies. In this paper, we review the mechanisms of action and functional importance of Tregs during the pathogenesis of IBD and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD. “Humanized” mouse models provide new tools to analyze human Treg ontogeny, immunobiology, and therapy and the role of Tregs in developing interventional strategies against IBD. Overall, humanized mouse models replicate the human conditions and prove a viable tool to study molecular functions of human Tregs to harness their therapeutic potential.

scholarly journals Development of an Inflammatory CD14+ Dendritic Cell Subset in Humanized Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Ryutaro Iwabuchi ◽  
Keigo Ide ◽  
Kazutaka Terahara ◽  
Ryota Wagatsuma ◽  
Rieko Iwaki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Cell Subset ◽  
Experimental Models ◽  
Transcriptional Analysis ◽  
Humanized Mice ◽  
Dendritic Cell Subset ◽  
Humanized Mouse ◽  
Gm Csf ◽  
Humanized Mouse Models

Humanized mouse models are attractive experimental models for analyzing the development and functions of human dendritic cells (DCs) in vivo. Although various types of DC subsets, including DC type 3 (DC3s), have been identified in humans, it remains unclear whether humanized mice can reproduce heterogeneous DC subsets. CD14, classically known as a monocyte/macrophage marker, is reported as an indicator of DC3s. We previously observed that some CD14+ myeloid cells expressed CD1c, a pan marker for bona fide conventional DC2 (cDC2s), in humanized mouse models in which human FLT3L and GM-CSF genes were transiently expressed using in vivo transfection (IVT). Here, we aimed to elucidate the identity of CD14+CD1c+ DC-like cells in humanized mouse models. We found that CD14+CD1c+ cells were phenotypically different from cDC2s; CD14+CD1c+ cells expressed CD163 but not CD5, whereas cDC2s expressed CD5 but not CD163. Furthermore, CD14+CD1c+ cells primed and polarized naïve CD4+ T cells toward IFN-γ+ Th1 cells more profoundly than cDC2s. Transcriptional analysis revealed that CD14+CD1c+ cells expressed several DC3-specific transcripts, such as CD163, S100A8, and S100A9, and were clearly segregated from cDC2s and monocytes. When lipopolysaccharide was administered to the humanized mice, the frequency of CD14+CD1c+ cells producing IL-6 and TNF-α was elevated, indicating a pro-inflammatory signature. Thus, humanized mice are able to sustain development of functional CD14+CD1c+ DCs, which are equivalent to DC3 subset observed in humans, and they could be useful for analyzing the development and function of DC3s in vivo.

scholarly journals Humanized Mouse Models for the Study of Periodontitis: An Opportunity to Elucidate Unresolved Aspects of Its Immunopathogenesis and Analyze New Immunotherapeutic Strategies

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina Rojas ◽  
Michelle P. García ◽  
Alan F. Polanco ◽  
Luis González-Osuna ◽  
Alfredo Sierra-Cristancho ◽  
...  
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Mouse Models ◽  
Time Window ◽  
Molecular Characteristics ◽  
Specific Response ◽  
Humanized Mouse ◽  
Immunodeficient Mice ◽  
Th17 Lymphocytes ◽  
Humanized Mouse Models

Periodontitis is an oral inflammatory disease in which the polymicrobial synergy and dysbiosis of the subgingival microbiota trigger a deregulated host immune response, that leads to the breakdown of tooth-supporting tissues and finally tooth loss. Periodontitis is characterized by the increased pathogenic activity of T helper type 17 (Th17) lymphocytes and defective immunoregulation mediated by phenotypically unstable T regulatory (Treg), lymphocytes, incapable of resolving the bone-resorbing inflammatory milieu. In this context, the complexity of the immune response orchestrated against the microbial challenge during periodontitis has made the study of its pathogenesis and therapy difficult and limited. Indeed, the ethical limitations that accompany human studies can lead to an insufficient etiopathogenic understanding of the disease and consequently, biased treatment decision-making. Alternatively, animal models allow us to manage these difficulties and give us the opportunity to partially emulate the etiopathogenesis of periodontitis by inoculating periodontopathogenic bacteria or by placing bacteria-accumulating ligatures around the teeth; however, these models still have limited translational application in humans. Accordingly, humanized animal models are able to emulate human-like complex networks of immune responses by engrafting human cells or tissues into specific strains of immunodeficient mice. Their characteristics enable a viable time window for the study of the establishment of a specific human immune response pattern in an in vivo setting and could be exploited for a wider study of the etiopathogenesis and/or treatment of periodontitis. For instance, the antigen-specific response of human dendritic cells against the periodontopathogen Porphyromonas gingivalis favoring the Th17/Treg response has already been tested in humanized mice models. Hypothetically, the proper emulation of periodontal dysbiosis in a humanized animal could give insights into the subtle molecular characteristics of a human-like local and systemic immune response during periodontitis and support the design of novel immunotherapeutic strategies. Therefore, the aims of this review are: To elucidate how the microbiota-elicited immunopathogenesis of periodontitis can be potentially emulated in humanized mouse models, to highlight their advantages and limitations in comparison with the already available experimental periodontitis non-humanized animal models, and to discuss the potential translational application of using these models for periodontitis immunotherapeutics.

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