Development and characterization of new flavivirus-resistant mouse strainsbearing Flv(r)-like and Flv(mr) alleles from wild or wild-derived mice

A single genetic locus, flavivirus resistance (Flv), controls virus titres and severity of flavivirus infection in mouse brain, It has been mapped to mouse chromosome 5 and shown to include different allelic forms, While the majority of laboratory mouse strains are susceptible to flaviviruses and ca rry the Flv(s) allele, wild mice and laboratory mouse strains recently deri ved from them are resistant and carry flavivirus-resistance alleles includi ng Flv(r)-like and Flv(mr) alleles, Although there is a mouse model of flav ivirus resistance conferred by the Flv(r) allele, other resistance alleles have not been adequately studied due to a lack of appropriate animal models , In this paper we describe the development of new flavivirus-resistant mou se strains, C3H.M.domesticus-Flv(r) and C3H.MOLD-Flv(mr), which carry the n ovel resistance alleles Flv(r)-like and Flv(mr) on the genetic background o f flavivirus susceptible C3H/HeJ mice, The new strains were created by 10 t o 11 generations of backcrossing followed by brother-sister matings resulti ng in a generation of homozygous founder stocks. Genome analysis of the new ly developed mouse strains has revealed chromosomal regions of approximatel y 9 and 11 cM, respectively, encompassing Flv on chromosome 5, which are de rived from resistant donor mice, These segments are much smaller than the s egment of approximately 31 cM described in the congenic resistant mouse str ain C3H.PRI-Flv(r) (also known as C3H/RV). The new congenic mouse strains, which were created to carry the Flv(r)-like and Flv(mr) alleles on the stan dardized genetic background of susceptible mice, represent new animal model s of flavivirus resistance conferred by these novel resistance alleles.