A novel small animal model for HIV‐1 infection

Ayash-Rashkovsky, Mila; Bentwich, Zvi; Arditti, Fabian D.; Friedman, Smadar Even Tov; Reisner, Yaīr; Borkow, Gadi

doi:10.1096/fj.04-3184fje

Cited by 10 publications

(4 citation statements)

References 39 publications

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“…Models include severe combined immune deficiency (SCID) mice that carry two mutated copies of the SCID gene (SCID/SCID mice) lack T-cells and B-cells and SCID/beige mice that also lack natural killer activity. Total body irradiation of BALB/c mice to destroy the haematopoietic system, followed by its replacement by engrafting bone-marrow samples from SCID mice results in the generation of mouse models capable of mounting primary and secondary cellular and humoral immune responses specific to a number of infections, including hepatitis B, hepatitis C and HIV (Ayash-Rashkovsky et al 2005). Such mouse models are additionally used as recipients for human tumour cell xenografts (Chang and Zhang 1995).…”

Section: Immunodeficiency Modelsmentioning

confidence: 99%

Genetically altered mice, man and medicine

Bhogal¹

2008

J Appl Biomed

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Several million genetically altered mice are used worldwide each year for research, toxicity testing, or simply to create or sustain mutant models. In fact, as our understanding of the genetic differences between mice and men improves, so does the drive to create mouse models of human disease and toxicity. However, while some models have proven to be useful and confer tangible benefits in terms of clinical management of disease, many others add little value to clinical medicine or human safety emphasising the need for a thorough investigation of the actual or future value of such models to human medicine.

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Section: Immunodeficiency Modelsmentioning

confidence: 99%

Genetically altered mice, man and medicine

Bhogal¹

2008

J Appl Biomed

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“…This, together with the successful use of Trimera mice as a tool for evaluating vaccines against Influenza and HBV (27,29,31,32), strongly supported the possibility that the Trimera mice can be used as a platform for HIV-1 infection and for studying and evaluating HIV-1 related vaccines and adjuvants. Indeed, a novel model for HIV-1 infection based on the Trimera mice has been recently described (33). Effective infection of Trimera mice was achieved with CXCR4 or CCR5-tropic HIV-1 laboratory strains or clinical isolates of different clades.…”

Section: Trimera -Hiv-1 Modelmentioning

confidence: 99%

“…Production of anti-HIV-1 IgM isotype Abs was followed by production of anti-HIV-1 IgG isotype Abs, and IFN-g was secreted by human T lymphocytes recovered from Trimera mice within the first month post-transplantation, following their in vitro exposure to an HIV-1 specific immunogen (33). Moreover, HIV-1 specific human immune responses, both humoral and cellular, were generated in noninfected Trimera mice, following their immunization with gp120-depleted HIV-1 antigen, presented by autologous human monocyte-derived DCs (34).…”

Section: Trimera -Hiv-1 Modelmentioning

confidence: 99%

Mouse models for HIV-1 infection

Borkow¹

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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The generation of small animal models, which preserve the ability for the generation of primary and memory immune responses of the engrafted human immune cells and in which a robust HIV‐1 infection may occur, may enable the rapid screening, development and evaluation of HIV‐1 protective vaccines and adjuvants. This manuscript reviews the existing mouse HIV‐1 models used to study virologic, immunologic and pathogenic aspects of HIV‐1 infection and disease and discusses their limitations and advantages, especially in the context of vaccine development, with special focus on the recently developed Trimera‐HIV‐1 animal model.

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“…Several studies have addressed these drawbacks by introducing a conditioning regimen that renders wild‐type (WT) BALB/c mice susceptible for human peripheral blood lymphocyte (hPBL) engraftment . Conditioning involved lethal total body irradiation (TBI) and subsequent radioprotection with bone marrow cells from immunodeficient NOD/SCID mice.…”

Section: Introductionmentioning

confidence: 99%

Comparison of three humanized mouse models for adoptive T cell transfer

Volk

Hartmann

Muik

et al. 2012

The Journal of Gene Medicine

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Background Humanized mouse models for adoptive T cell transfer are important for preclinical efficacy and toxicity studies. However, common xenograft models using immunodeficient mice have so far failed to efficiently support the homing of human T cells to secondary lymphoid tissues. Methods We established a new mouse model for the adoptive transfer of genetically‐modified (gm) T cells using conditioned BALB/c mice. Conditioning involved cyclophosphamide injections, lethal irradiation and radioprotection with bone marrow from immunodeficient mice. We compared repopulation kinetics and the quality of grafts in these modified Trimera (mT3) mice with immunodeficient BALB/c Rag2−/− interleukin (IL)2 receptor gamma (rg) knockout (DKO) and NOD/LtSz‐scid IL2rg−/− (NSG) recipient mouse strains. Results DKO mice showed only marginal engraftment until onset of graft‐versus‐host disease, whereas mT3 and NSG were repopulated with comparable kinetics. However, T cell repertoire and human cytokine profiles suggest a xenoreactivity‐driven gm T cell expansion in mT3 mice, whereas NSG mice were characterized by an initial homeostatic proliferation. Morphological analysis revealed high levels of human gm T cell infiltration in the spleen and liver of all three mouse strains. However, mT3 mice provided the strongest homing of human gm T cells to mucosal sites. Additionally, mT3 mice were the only model with macroscopically visible superficial inguinal lymph nodes. These lymph nodes strongly supported the homing of gm T cells. Conclusions In the present study, we give proof‐of‐concept that wild‐type mice can accept gm T cell grafts while providing secondary lymphoid structures. Despite limitations, mT3 mice are a valid alternative for applications that specifically rely on improved secondary lymphoid structures. Copyright © 2012 John Wiley & Sons, Ltd.

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A novel small animal model for HIV‐1 infection

Cited by 10 publications

References 39 publications

Genetically altered mice, man and medicine

Genetically altered mice, man and medicine

Mouse models for HIV-1 infection

Comparison of three humanized mouse models for adoptive T cell transfer

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