| First Author | Sangster MY | Year | 1991 |
| Journal | Mouse Genome | Volume | 89 |
| Issue | 4 | Pages | 849-850 |
| Mgi Jnum | J:1613 | Mgi Id | MGI:50140 |
| Citation | Sangster MY, et al. (1991) Genetically controlled resistance to flaviviruses in mice: allelism at the Flv locus. Mouse Genome 89(4):849-850 |
| abstractText | Full text of Mouse Genome contribution: RESEARCH NEWS: Genetically controlled resistance to flaviviruses in mice: allelism at the Flv locus. Resistance to flavivirus infection has been recognised as an inherited trait in only four strains of laboratory mice, namely, Det (Lynch and Hughes, 1931), BSVR and BRVR (Webster, 1937) and PRI (Sabin, 1952). In PRI mice, resistance was attributed to a single autosomal dominant gene (now designated Flvr) which was introduced into the flavivirus Ðsusceptible C3H/He strain to produce the congenic flavivirus-resistant C3H/RV (C3H.PRI-Flvr) strain (Groschel and Koprowski, 1965). The Flvr gene and the susceptibility allele (Flvs) reside at the unmapped Flv locus (Green, 1989). Because the Flvr gene limits the growth of flaviviruses in all target cells, including the cells of the central nervous sytem, the presence of the Flvr gene protects mice against doses of flaviviruses which would otherwise be lethal (Brinton, 1981). We have screened a number of inbred mouse strains for the presence of the Flvr gene by determining the lethality of intracerebral flavivirus infection and by measuring flavivirus replication in the brain. The strains tested were compared to the C3H-HeJ (Flvs/Flvs) and the C3H/RV (Flvr/Flvr) inbred strains. Included in this study were two inbred strains, CASA/Rk and MOLD/Rk, which were recently derived from wild M. m. castaneus and M.m. molossinus, respectively (Roderick, 1982). The inbred strains A/J, AKR/Lac, BALB/cJLac, C57BL/6J, C57BL/10ScSn, CBA/CaH, CE/J, DBA/2J, I/M, LP.R111, NZW, R111 (substrain unknown; mice obtained from the Cancer Institute, Melbourne) and SJL/J could not be distinguished from C3H/HeJ mice, a result which supports the conclusion of Darnell et a1 (1974) that the Flvr gene is absent from commonly used inbred strains of laboratory mice. However, both the CASA/Rk and MOLD/Rk strains were more resistant than C3H/HeJ mice. The outcome of lethality and replication studies showed that the resistance of the CASA/Rk strain resembled the resistance of C3H/RV mice. Both of these strains survived infection with the flaviviruses Murray Valley encephalitis (MVE) virus and yellow fever (YF) virus (see table l). In contrast, the resistance of the MOLD/Rk strain was of a lesser magnitude, since it protected only against infection with YF virus, a flavivirus of relatively low virulence in mice. The results of virus replication studies also support the conclusion that the flavivirus resistance of the MOLD/Rk strain is intermediate between that of C3H/RV and C3H/HeJ mice. Table 1: The mortality in inbred mouse strains infected with MVE virus or YF virus.* Mouse strain: CASA/Rk; MVE Virus: 15 (2/13); Mortality (%): YF Virus: 0 (0/14). Mouse strain: MOLD/Rk; MVE Virus: 100 (20/20); Mortality (%): YF Virus: 4 (1/26). Mouse strain: C3H/HeJ; MVE Virus: 100 (9/9); Mortality (%): YF Virus: 85 (11/13). Mouse strain: C3H/RV; MVE Virus: 0 (0/10); Mortality (%): YF Virus: 0 (0/12). * Adult mice were infected by the i.c. route with virus doses equivalent to 10(3) i.c. LD50 for C3H/HeJ mice. Inheritance studies using C3H/HeJ mice as the susceptible parent were undertaken to investigate a genetic basis for the resistance of the CASA/Rk strain to MVE virus and the resistance of the MOLD/Rk strain to YF virus. Following infection with MVE virus, the mortality was 0% in male and female (C3H/HeJ x CASA/Rk)F1, 58% in backcrosses to C3H/HeJ and 26% in F2. Infection with YF virus produced mortalities of 0% in male and female (C3H/HeJ x MOLD/Rk)F1, 42% in backcrosses to C3H/HeJ and 21% in F2. These results indicate that resistance in the CASA/Rk and MOLD/Rk strains is conferred by single autosomal dominant genes. In the heterozygous state, the CASA/Rk resistance gene was like Flvr and protected against infection with both MVE virus and YF virus, whereas the MOLD/Rk resistance gene protected only against YF virus. Tests for allelism with Flvr were positive for the resistance genes in both the CASA/Rk and MOLD/Rk strains. We conclude that flavivirus resistance in the CASA/Rk strain is due to a gene which is similar or identical to Flvr, whereas a previously undescribed allele at the Flv locus confers resistance to flaviviruses in the MOLD/Rk strain. For the MOLD/Rk resistance gene we propose the symbol Flvmr to indicate minor resistance to flavivirus infection. References Brinton, M.A. (1981) Curr. Top. Microbiol. Immunol. 92:1-14. Darnell, M.B., Koprowski, H. and Lagerspetz, K. (1974) J. Infect. Dis. 129: 240-247. Green, M.C. (1989) In: Genetic Variants and Strains of the Laboratory Mouse, 2nd ed. (Lyon, M.F. and Searle, A.G., eds) Oxford University Press, Oxford, pp 12-403. Groschel, D. and Koprowski, H. (1965) Arch. ges. Virusforsch. 17: 379-391. Lynch, C.J. and Hughes, T.P. (1936) Genetics 21: 104-112. Roderick, T.H. (1982) Mouse News Lett. 67: 22-23. Sabin, A.B. (1952) Ann. N.Y. Acad. Sci. 54: 936-944. Webster, L.T. (1937) J. Exp. Med. 65: 261-286. |
