SUSCEPTIBILITY OF NUDE-MICE CARRYING THE FV-4 GENE TO FRIEND MURINE LEUKEMIA-VIRUS INFECTION

Fv-4 is a mouse gene that dominantly confers resistance to infection w ith Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med . 45:473-478, 1975). Despite complete resistance to ecotropic MuLV inf ection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance a s extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-46 3, 1978). To investigate the immunological effect on resistance in viv o, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4(-/-) nude(n u/nu)) by mating them with Fv-4 congenic BALB/c mice (Fv(-r/r) nude(+/ +)) and examined the susceptibility of the F-2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4(-/-) nude(nu/nu)) were pe rmissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4(r/r) nude(nu/nu)) did not develop leukemia, and no or little virus was dete cted in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F-1 mice w ith the FV-4(r/-) nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F-1 mice with the Fv-4(r/-) nude(+/+) genotype. Howe ver, almost all BALB/c nude mice with the Fv-4(r/-) nude(nu/nu) genoty pe developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia, These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fc-4 product.