USP44 is dispensable for normal hematopoietic stem cell function, lymphocyte development, and B-cell-mediated immune response in a mouse model

Abstract

Ubiquitin-specific protease 44 (USP44) is a nuclear protein with deubiquitinase (DUB) catalytic activity that has been implicated as an important regulator of cell cycle progression, gene expression, and genomic stability. Dysregulation in the molecular machinery controlling cell proliferation, gene expression, and genomic stability in human or mouse is commonly linked to hematopoietic dysfunction, immunodeficiency, and cancer. We therefore set out to explore the role of USP44 in hematopoietic and immune systems through characterization of a Usp44-deficient mouse model. We report that USP44 is dispensable for the maintenance of hematopoietic stem cell numbers and function under homeostatic conditions, and also after irradiation or serial transplantation. USP44 is also not required for normal lymphocyte development. Usp44-deficient B cells show normal activation, proliferation, and immunoglobulin class switching in response to in vitro stimulation, and Usp44-deficient mice mount normal antibody response to immunization. We also tested the effects of USP44 deficiency on disease progression and survival in the Emu-myc model of mouse B-cell lymphoma and observed a trend toward earlier lethality of Usp44-/- Emu-myc mice; however, this did not reach statistical significance. Overall, we conclude that USP44 is dispensable for the normal physiology of hematopoietic and immune systems, and its functions in these systems are likely redundant with other USP family proteins.