PSMB10 and severe combined immunodeficiency: In a large-scale mouse N-ethyl-N-nitrosourea (ENU) mutagenesis and phenotypic screening approach, aimed at discovering mutant mouse lines with clinical phenotypes as models for human diseases31, we identified the single amino acid substitution G170W in the proteasome subunit MECL-1 to cause severe combined immunodeficiency (SCID) and systemic autoinflammation.