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 (Flv(r)). A positional cloning strategy followed by comparison of F/v interval gene sequences from congenic resistant C3H.PRI-F/v(r) and susceptible C3H/He mouse strains identified the 2'-5'-oligoadenylate synthetase lb (Oas] b) 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 Oaslb resistance allele into a susceptible mouse strain produced mice with the flavivirus resistance phenotype, confirming that this phenotype is mediated by a single gene. (c) 2007 Elsevier Inc. All rights reserved.