Humanized Mice for Infectious and Neurodegenerative disorders

Abstract

Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.

Molecular and anatomical roadmap of stroke pathology in immunodeficient mice

“…Alternatively, future studies may use immune deficient mice such as NSG or Rag2 -/- Il2 -/- and CD47 -/- (Tripple KO) mice that are reconstituted with a humanised immune system and HLA-matched to the donor cells. Humanised mice may show a closer pathology to the WT [27], although these mice still have several limitations, including limited lifespan, incomplete human immune function and graft-versus-host disease etc [28].…”

Recent Developments in NSG and NRG Humanized Mouse Models for Their Use in Viral and Immune Research

“…Consequently, HIV-1 subgenomic DNA was eliminated in vivo and could not be further detected in blood, lymphoid tissue, bone marrow, or brain. These results showed the possibility of permanent virus elimination in human patients [ 97 , 98 ].…”

Animal models for studies of HIV-1 brain reservoirs

“…To date, humanized mice with a human hematolymphoid system have been used to study HIV persistence in the brain and its associated neuropathology 83–87 . Immune deficient mice that are engrafted with a human immune system can reflect HIV‐associated brain diseases seen in humans 84,87–89 . A model known as HIV encephalitis mice was created by injecting HIV‐infected monocyte‐derived macrophages into the basal ganglia of humanized mice, and this model showed many of the hallmark signs of HIV infection in the brain, such as neuronal death, neurocognitive impairment, and the activation of microglia 60 .…”

“… 83 , 84 , 85 , 86 , 87 Immune deficient mice that are engrafted with a human immune system can reflect HIV‐associated brain diseases seen in humans. 84 , 87 , 88 , 89 A model known as HIV encephalitis mice was created by injecting HIV‐infected monocyte‐derived macrophages into the basal ganglia of humanized mice, and this model showed many of the hallmark signs of HIV infection in the brain, such as neuronal death, neurocognitive impairment, and the activation of microglia. 60 In another NSG‐humanized mouse model, behavioral changes were observed after HIV infection, which also displayed neuronal damage as measured using magnetic resonance spectroscopy and validated using immunofluorescence.…”