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- W2949431301 abstract "Abstract Background The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases, like HIV-1, and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase ( CMAH ) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes of mouse glycoproteins chemistry will affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection is not known. Results We mutated mouse CMAH on the most widely human cells transplantation strain NOD/scid-IL2Rγ c -/- (NSG) mouse background using the CRISPR/Cas9 system. The new strain provides a better environment for human immune cells. Transplantation of human hematopoietic stem cells leads to broad B cells repertoire, higher sensitivity to HIV-1 infection, and enhanced proliferation of transplanted peripheral blood lymphocytes. The mice showed low effects on the clearance of human immunoglobulins and enhanced transduction efficiency of recombinant adeno-associated viral vector rAAV2/DJ8. Conclusion NSG- cmah -/- mice expand the mouse models suitable for human cells transplantation and this new model has advantages in generating a human B cell repertoire. This strain is suitable to study different aspects of the human immune system development, might provide advantages in patient-derived tissue and cell transplantation, and could allow studies of viral vectors and infectious agents that are sensitive to human-like sialylation of mouse glycoproteins." @default.
- W2949431301 created "2019-06-27" @default.
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- W2949431301 date "2018-08-31" @default.
- W2949431301 modified "2023-09-26" @default.
- W2949431301 title "Human-like NSG mouse glycoproteins sialylation pattern changes the phenotype of human lymphocytes and sensitivity to HIV-1 infection" @default.
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- W2949431301 doi "https://doi.org/10.1101/404905" @default.
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