An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence.
Here we describe a previously unknown form of inherited immunodeficiency revealed by an N-ethyl-N-nitrosourea-induced mutation called elektra. Mice homozygous for this mutation showed enhanced susceptibility to bacterial and viral infection and diminished numbers of T cells and inflammatory monocytes that failed to proliferate after infection and died via the intrinsic apoptotic pathway in response to diverse proliferative stimuli. They also had a greater proportion of T cells poised to replicate DNA, and their T cells expressed a subset of activation markers, suggestive of a semi-activated state. We positionally ascribe the elektra phenotype to a mutation in the gene encoding Schlafen-2 (Slfn2). Our findings identify a physiological role for Slfn2 in the defense against pathogens through the regulation of quiescence in T cells and monocytes.
Pubmed ID: 20190759 RIS Download
Animals | Apoptosis | Base Sequence | Cell Cycle Proteins | Cell Separation | Flow Cytometry | Immunologic Deficiency Syndromes | Leukocytes, Mononuclear | Lymphocyte Activation | Mice | Mice, Transgenic | Mutation | Phenotype | Signal Transduction | T-Lymphocytes