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- W2773732645 abstract "The objectives of this work were to generate new immunodeficient rat models. The rat is an important experimental model for studying human physiopathology and testing novel therapeutic approaches. Immune responses, however, are often an obstacle, such as in organ and cell transplantation using human iPS/ES-derived cells for regenerative medicine, hematopoietic stem cells for humanization of the immune system, gene therapy and cancer biology. Thus, a readily available, non-commercial source of immunodeficient rats would be useful. Rats KO for IgM, Rag1 or IL2Rg were generated using microinjection into zygotes of either zinc finger nucleases, meganucleases or TALE nucleases, respectively. IgM KO rats showed undetectable serum levels of IgM, IgG, IgA and IgE. B cells (B220+) in spleen and bone marrow were 99% and 90% reduced vs. controls and had a pro-B cell developmental block. T cells in lymph nodes were normal but reduced in the spleen. Both RAG1 and IL2Rg KO rats showed drastically reduced thymus, lymph nodes and spleen and the number of cells in these organs and in bone marrow were decreased between 98 and 77%. In spleen and lymph nodes, RAG1 KO rats showed > 92 % reduced numbers of T CD4+, T CD8+ and B cells with conserved numbers of NK cells and macrophages. In IL2Rg KO rats, the proportion of T CD4+, CD8+ and NK cells were reduced > 90%, whereas B cells were reduced by 70%. Serum IgG, IgA and IgE were inhibited > 70% in RAG1- and in IL2Rg-deficient rats. Allogeneic organ transplantation in RAG1 KO rats showed significant delay in rejection vs. controls and similar experiments are under way with IL2Rg KO rats. Human tumor growth was observed in IL2Rg KO rats and similar experiments are under way in RAG1 KO rats. IL2Rg- and RAG1 KO rats are being crossed to obtain profoundly immunosuppressed double KO animals for studies in areas such as stem-cell medicine, transplantation and cancer biology. DISCLOSURES:Fraichard, A.: Employee, Genoway. Buelow, R.: Stockholder, Open Monoclonal Technology, Inc." @default.
- W2773732645 created "2017-12-22" @default.
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- W2773732645 date "2014-07-01" @default.
- W2773732645 modified "2023-10-18" @default.
- W2773732645 title "Generation and Characterization of IgM, Rag1 and/or ILR2g knockout Immunodeficient Rats." @default.
- W2773732645 doi "https://doi.org/10.1097/00007890-201407151-01325" @default.
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