Knock-in of the Oas1br allele into a flavivirus-induced disease susceptible mouse generates the resistant phenotype

Inheritance patterns in mice suggested that resistance to flavivirus-induced disease was conferred by a single autosomal dominant allele (Flvr). A positional cloning strategy followed by comparison of Flv interval gene sequences from congenic resistant C3H.PRI-Flvr and susceptible C3H/He mouse strains identified the 2′–5′-oligoadenylate synthetase 1b (Oas1b) gene as Flv. However, since these mouse strains differ by a 31 cM region, the possible involvement of differences in other linked genes in the resistant phenotype could not be absolutely ruled out. Knock-in of the Oas1b resistance allele into a susceptible mouse strain produced mice with the flavivirus resistance phenotype, confirming that this phenotype is mediated by a single gene.