New generation humanized mice for virus research: Comparative aspects and future prospects

Akkina, Ramesh

doi:10.1016/j.virol.2012.10.007

Cited by 171 publications

(168 citation statements)

References 159 publications

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“…Currently the hu-BLT mouse model has been used mostly to study HIV-1 and a limited number of other viruses (9,(11)(12)(13)(14). Little is known whether this model can be used to study KSHV infection, for which there is no good small-animal model to study its infection and disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Wang

Kang

Kumar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Lack of an effective small-animal model to study the Kaposi's sarcoma-associated herpesvirus (KSHV) infection in vivo has hampered studies on the pathogenesis and transmission of KSHV. The objective of our study was to determine whether the humanized BLT (bone marrow, liver, and thymus) mouse (hu-BLT) model generated from NOD/SCID/IL2rγ mice can be a useful model for studying KSHV infection. We have tested KSHV infection of hu-BLT mice via various routes of infection, including oral and intravaginal routes, to mimic natural routes of transmission, with recombinant KSHV over a 1-or 3-mo period. Infection was determined by measuring viral DNA, latent and lytic viral transcripts and antigens in various tissues by PCR, in situ hybridization, and immunohistochemical staining. KSHV DNA, as well as both latent and lytic viral transcripts and proteins, were detected in various tissues, via various routes of infection. Using double-labeled immune-fluorescence confocal microscopy, we found that KSHV can establish infection in human B cells and macrophages. Our results demonstrate that KSHV can establish a robust infection in the hu-BLT mice, via different routes of infection, including the oral mucosa which is the most common natural route of infection. This hu-BLT mouse not only will be a useful model for studying the pathogenesis of KSHV in vivo but can potentially be used to study the routes and spread of viral infection in the infected host. T he Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as the human herpesvirus 8, was first identified from KS tissues in 1994 (1). It is the etiologic agent for KS and is also associated with primary effusion lymphoma (PEL) and multicentric Castleman's disease (2). More recently it was also found to be associated with KSHV-associated inflammatory cytokine syndrome (3). Although substantial progress has been made in characterizing the virus, there are still many unanswered questions such as how KSHV infection can lead to disease manifestation and whether latent or lytic induction of KSHV are associated with malignancies. One of the reasons is a lack of a good small-animal model to study KSHV infection in vivo, which has hampered studies on how KSHV infects, spreads, and how it interacts with the host and ultimately leads to disease pathogenesis. Moreover, currently there is no vaccine against KSHV infection, and there is need for an effective animal model to evaluate the efficacy of vaccines if they are developed and for the testing of antiviral regimens.An ideal model should have relatively short generation time, reproduce rapidly, be inexpensive to maintain and house, and be easy to manipulate. An example is a rodent model that can be infected by KSHV effectively. Several small-rodent models have been tested for KSHV infection. The models include transplantation with both human KSHV-infected B lymphoma cells and primary human peripheral blood mononuclear cells in the SCID mouse (4), injection of KSHV into the human skin engrafted or the transplant of the SCID mice...

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Section: Discussionmentioning

confidence: 99%

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Wang

Kang

Kumar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…For a comprehensive overview of the history and use of xenografting, the reader is directed to a number of recent reviews. [1][2][3][4][5] In this review, we will focus on the models and approaches of most relevance to researchers studying normal and malignant hematopoiesis and discuss future avenues to take that will address current limitations.…”

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confidence: 99%

“…For example, the humanized mouse, in which components of human bone marrow (BM), liver, and thymus (BLT) are grafted in immunodeficient mice, is most popular with investigators studying infectious disease due to the faithful development of mature, properly educated human T cells and a more complete, functional human immune system. 5,8 The BLT approach is powerful but requires specialized surgical expertise and additional time, as well as tissue from human fetuses, raising feasibility issues. For studying hematologic malignancies, many researchers use the NSG mouse expressing cytokines that support human myelopoiesis (NSG-hSCF, hGM-CSF, hIL3, all driven from the cytomegalovirus promoter; NSGS), for their superiority in promoting robust engraftment of a wide range of patient samples.…”

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confidence: 99%

Xenograft models for normal and malignant stem cells

Goyama

Wunderlich

Mulloy

2015

Blood

113

101

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The model systems available for studying human hematopoiesis, malignant hematopoiesis, and hematopoietic stem cell (HSC) function in vivo have improved dramatically over the last decade, primarily due to improvements in xenograft mouse strains. Several recent reviews have focused on the historic development of immunodeficient mice over the last 2 decades, as well as their use in understanding human HSC and leukemia stem cell (LSC) biology and function in the context of a humanized mouse. However, in the intervening time since these reviews, a number of new mouse models, technical approaches, and scientific advances have been made. In this review, we update the reader on the newest and best models and approaches available for studying human malignant and normal HSCs in immunodeficient mice, including newly developed mice for use in chemotherapy testing and improved techniques for humanizing mice without laborious purification of HSC. We also review some relevant scientific findings from xenograft studies and highlight the continued limitations that confront researchers working with human HSC and LSC in vivo. (Blood. 2015;125(17):2630-2640 Immunodeficient mice for studying normal and malignant human hematopoiesisSince immunodeficient mice were first used in biomedical research, there has been a continual effort to improve their utility and expand their applicability to more areas of research. Over the last decade, with the advent of widespread transgenic approaches and the understanding by researchers of the potential for these models in moving our understanding of biology forward, a number of genetically engineered animals have become available. For a comprehensive overview of the history and use of xenografting, the reader is directed to a number of recent reviews.

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“…If speciesspecific factors are subject of research, one possible bypass is the use of humanized mouse acceptors. Humanized substrains of NSG and NOG expressing species-specific human cytokines, growth factors, receptors, histocompatibility antigens or adhesion molecules, or harboring even functional human hematopoietic stem cells or tissues such as bone marrow, liver, and thymus are under development to address questions related to human immune cells and stem cells within their niche (39,41) as well as virus (EBV and HCV)-related aspects of cancer (42). In contrast, syngeneic, immune-compatible transplanted cells are not rejected by the host organism.…”

Section: Cell-based Transplantation Modelsmentioning

confidence: 99%

Models in Translational Oncology: A Public Resource Database for Preclinical Cancer Research

et al. 2017

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The devastating diseases of human cancer are mimicked in basic and translational cancer research by a steadily increasing number of tumor models, a situation requiring a platform with standardized reports to share model data. Models in Translational Oncology (MiTO) database was developed as a unique Web platform aiming for a comprehensive overview of preclinical models covering genetically engineered organisms, models of transplantation, chemical/physical induction, or spontaneous development, reviewed here. MiTO serves data entry for metastasis profiles and interventions. Moreover, cell lines and animal lines including tool strains can be recorded. Hyperlinks for connection with other databases and file uploads as supplementary information are supported. Several communication tools are offered to facilitate exchange of information. Notably, intellectual property can be protected prior to publication by inventordefined accessibility of any given model. Data recall is via a highly configurable keyword search. Genome editing is expected to result in changes of the spectrum of model organisms, a reason to open MiTO for species-independent data. Registered users may deposit own model fact sheets (FS). MiTO experts check them for plausibility. Independently, manually curated FS are provided to principle investigators for revision and publication. Importantly, noneditable versions of reviewed FS can be cited in peer-reviewed journals.

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New generation humanized mice for virus research: Comparative aspects and future prospects

Cited by 171 publications

References 159 publications

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Xenograft models for normal and malignant stem cells

Models in Translational Oncology: A Public Resource Database for Preclinical Cancer Research

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