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• W4313703408 abstract "Abstract Myb-like SWIRM and MPN domains 1 (MYSM1) is a chromatin binding protein with deubiquitinase (DUB) catalytic activity. Rare MYSM1 mutations in human patients result in an inherited bone marrow failure syndrome, highlighting the biomedical significance of MYSM1 in the hematopoietic system. We and others characterized Mysm1 -knockout mice as a model of this disorder and established that MYSM1 regulates hematopoietic function and leukocyte development in such models through different mechanisms. It is, however, unknown whether the DUB catalytic activity of MYSM1 is universally required for its many functions and for the maintenance of hematopoiesis in vivo. To test this, here we generated a new mouse strain carrying a Mysm1 D660N point mutation ( Mysm1 DN ) and demonstrated that the mutation renders MYSM1 protein catalytically inactive. We characterized Mysm1 DN/DN and Mysm1 fl/DN Cre ERT2 mice, against appropriate controls, for constitutive and inducible loss of MYSM1 catalytic function. We report a profound similarity in the developmental, hematopoietic, and immune phenotypes resulting from the loss of MYSM1 catalytic function and the full loss of MYSM1 protein. Overall, our work for the first time establishes the critical role of MYSM1 DUB catalytic activity in vivo in hematopoiesis, leukocyte development, and other aspects of mammalian physiology." @default.
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• W4313703408 date "2023-01-07" @default.
• W4313703408 modified "2023-10-01" @default.
• W4313703408 title "Deubiquitinase catalytic activity of MYSM1 is essential in vivo for hematopoiesis and immune cell development" @default.
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• W4313703408 doi "https://doi.org/10.1038/s41598-023-27486-7" @default.
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