Check your mice: a point mutation in the Ncr1 locus identified in CD45.1 congenic mice with consequences on mouse susceptibility to infection

Abstract

B6.SJL-Ptprc ^aPepc ^b/Boy (CD45.1) mice have been used in hundreds of congenic competitive transplants, with the presumption that they differ from B6 mice only at the CD45 locus. In this study, we describe a point mutation in the Ncr1 locus fortuitously identified in the CD45.1 strain. This point mutation was mapped at the 40 ^th nucleotide of the Ncr1 locus causing a single amino acid mutation from cysteine to arginine at position 14 from start codon, resulting in loss of NCR1 expression. We found that these mice were more resistant to cytomegalovirus due to a hyper innate IFNγ response in the absence of NCR1. In contrast, loss of NCR1 increased susceptibility to Influenza virus, a result which is consistent with the role of NCR1 in the recognition of influenza antigen, hemagglutinin. This work shed light on potential confounding experimental interpretation if this congenic strain is used as a tool for tracking lymphocyte development.