Abstract
Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R−/− (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat’s remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.
Highlights
Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens
The study of bat biology is limited due to reasons such as, (1) wild bats of the same genetic lineage may express a wide variation in their response to the same stimulus, (2) due to conservation and ethical reasons, species of interest cannot be captured from the wild freely and/or in large numbers[15], (3) with innate instincts of setting up maternity colonies, it is extremely challenging to breed bats within an animal facility and their reproduction rate is much lower than rodents[16]
Transplantation of bat bone marrow (BM) cells led to stable reconstitution of bat immune cells in NSG recipients
Summary
Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. The establishment of a targeted mutation in the IL-2 receptor common gamma chain gene (IL-2Rγ−/−) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues[28], effectively creating human immune systems within an immunodeficient mice[24,29,30] These humanized mice are becoming increasingly important as pre-clinical models for a range of studies, especially research concerning human-specific immune responses to infectious agents and drugs[28,30,31]
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