Are rats more human than mice?

Wildner, Gerhild

doi:10.1016/j.imbio.2018.09.002

Cited by 34 publications

(28 citation statements)

References 59 publications

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“…The immune system of rats have several characteristics that make them more similar to humans than mice (21) and the recent generation of many gene edited rats (22) will allow to cross Foxp3-EGFP rats with other mutated strains to analyze the role of Treg in these models.…”

Section: Discussionmentioning

confidence: 99%

“…The immune system of rats have several characteristics that make them more similar to humans than mice, such as expression of MHC-II molecules by T cells, CD4 expression by a subset of DCs and normal levels of complement (21, 22). Additionally, certain human immune diseases are better modelized in rat than in mouse models with the same genetic mutations (22), such as for ankylosing spondylopathy (23) and autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) (24), in HLA-B27 transgenic and in Aire knockout rats, respectively.…”

Section: Introductionmentioning

confidence: 99%

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CD4⁺and CD8⁺regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

Ménoret

Tesson

Remy

et al. 2021

Preprint

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Background: CD4+ and CD8+ regulatory T cells (Treg) in diverse species include different subsets from different origins. In all species, CD8+ Treg have been poorly characterized. CD4+ and CD8+ Treg in rats have only partially been characterized and there is no rat model in which FOXP3+ Treg are genetically tagged. Results: We generated a rat transgenic line using the CRISPR/Cas9 system in which EGFP was inserted in frame on the 3 end of the Foxp3 gene using a 2A self-cleaving peptide. EGFP was exclusively expressed by CD4+ and CD8+ T cells in similar proportion as observed with anti-FOXP3 antibodies. CD4+EGFP+ Treg were 5-10 times more frequent than CD8+EGFP+ Treg. CD4+ and CD8+ EGFP+ Treg expressed both the CD25highCD127lowCD45RClow/- markers. The suppressive activity of CD4+ and CD8+ Treg was largely confined to EGFP+ cells. RNAseq analyses showed similarities but also differences among CD4+ and CD8+ EGFP+ cells and provided the first description of the natural FOXP3+ CD8+ Treg transcriptome. In vitro culture of CD4+ and CD8+ EGFP- cells with TGFbeta and IL-2 resulted in the induction of EGFP+ Treg. Preferential expansion of CD4+ and CD8+ EGFP+ Treg could be detected upon in vivo administration of a low dose of IL-2. Conclusions: This new and unique Foxp3-EGFP rat line constitutes a useful model to identify and isolate viable natural and induced CD4+ and CD8+ Treg. Additionally, it allows to identify new molecules expressed in CD8+ Treg that may allow to better define their phenotype and function not only in rats but also in other species.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD4⁺and CD8⁺regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

Ménoret

Tesson

Remy

et al. 2021

Preprint

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“…In general terms, rats share more immune characteristics with humans than mice do (Wildner, 2019). As an example, complement levels in humans and rats are comparable (Ong and Mattes, 1989;Ménoret et al, 2020), whereas in most inbred mouse strains, they are undetectable or very low because of different genetic mutations (Ong and Mattes, 1989;Wetsel et al, 1990;Shultz et al, 1995).…”

Section: Models To Study Genes Of the Immune Systemmentioning

confidence: 99%

Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models

et al. 2021

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The rat has been extensively used as a small animal model. Many genetically engineered rat models have emerged in the last two decades, and the advent of gene-specific nucleases has accelerated their generation in recent years. This review covers the techniques and advances used to generate genetically engineered rat lines and their application to the development of rat models more broadly, such as conditional knockouts and reporter gene strains. In addition, genome-editing techniques that remain to be explored in the rat are discussed. The review also focuses more particularly on two areas in which extensive work has been done: human genetic diseases and immune system analysis. Models are thoroughly described in these two areas and highlight the competitive advantages of rat models over available corresponding mouse versions. The objective of this review is to provide a comprehensive description of the advantages and potential of rat models for addressing specific scientific questions and to characterize the best genome-engineering tools for developing new projects.

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“…Kidney organoids successfully contain organized compartments dedicated to nephrons, collecting ducts, stroma, and an endothelial network. 111 Human kidney organoids can be transplanted into NSG mice, where they join onto the murine vasculature and undergo glomerular and tubular epithelium maturation. 112 …”

Section: Micementioning

confidence: 99%

Humanization of Immunodeficient Animals for the Modeling of Transplantation, Graft Versus Host Disease, and Regenerative Medicine

et al. 2020

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The humanization of animals is a powerful tool for the exploration of human disease pathogenesis in biomedical research, as well as for the development of therapeutic interventions with enhanced translational potential. Humanized models enable us to overcome biologic differences that exist between humans and other species, while giving us a platform to study human processes in vivo. To become humanized, an immune-deficient recipient is engrafted with cells, tissues, or organoids. The mouse is the most well studied of these hosts, with a variety of immunodeficient strains available for various specific uses. More recently, efforts have turned to the humanization of other animal species such as the rat, which offers some technical and immunologic advantages over mice. These advances, together with ongoing developments in the incorporation of human transgenes and additional mutations in humanized mouse models, have expanded our opportunities to replicate aspects of human allotransplantation and to assist in the development of immunotherapies. In this review, the immune and tissue humanization of various species is presented with an emphasis on their potential for use as models for allotransplantation, graft versus host disease, and regenerative medicine.

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Are rats more human than mice?

Cited by 34 publications

References 59 publications

CD4⁺and CD8⁺regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

CD4⁺and CD8⁺regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models

Humanization of Immunodeficient Animals for the Modeling of Transplantation, Graft Versus Host Disease, and Regenerative Medicine

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Are rats more human than mice?

Cited by 34 publications

References 59 publications

CD4+and CD8+regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

CD4+and CD8+regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models

Humanization of Immunodeficient Animals for the Modeling of Transplantation, Graft Versus Host Disease, and Regenerative Medicine

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CD4⁺and CD8⁺regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel

CD4⁺and CD8⁺regulatory T cells characterization in the rat using a unique transgenicFoxp3-EGFPmodel