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

• Published in: Journal of general virology Vol. 80; no. 4; pp. 897 - 906
• Main Authors: Urosevic, N, Silvia, O J, Sangster, MY, Mansfield, J P, Hodgetts, SI, Shellam, G R
• Format: Journal Article
• Language: English
• Published: 01-04-1999
• Subjects: Flavivirus; Mus domesticus
• ISSN: 0022-1317

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 carry the Flv super(s) allele, wild mice and laboratory mouse strains recently derived from them are resistant and carry flavivirus-resistance alleles including Flv super(r)-like and Flv super(mr) alleles. Although there is a mouse model of flavivirus resistance conferred by the Flv super(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 mouse strains, C3H.M.domesticus-Flv super(r) and C3H.MOLD-Flv super(mr), which carry the novel resistance alleles Flv super(r)-like and Flv super(mr) on the genetic background of flavivirus susceptible C3H/HeJ mice. The new strains were created by 10 to 11 generations of backcrossing followed by brother-sister matings resulting in a generation of homozygous founder stocks. Genome analysis of the newly developed mouse strains has revealed chromosomal regions of approximately 9 and 11 cM, respectively, encompassing Flv on chromosome 5, which are derived from resistant donor mice. These segments are much smaller than the segment of approximately 31 cM described in the congenic resistant mouse strain C3H.PRI-Flv super(r) (also known as C3H/RV). The new congenic mouse strains, which were created to carry the Flv super(r)-like and Flv super(mr) alleles on the standardized genetic background of susceptible mice, represent new animal models of flavivirus resistance conferred by these novel resistance alleles.