Host genetic determinants of neurological disease induced by Cas-Br-M murine leukemia virus.
Cas-Br-M is an ecotropic murine leukemia virus (MuLV) of wild-mouse origin that causes neurogenic hind-limb paralysis. By virtue of its N-tropism, the virus replicates well in tissues of mice bearing the n but not the b allele at the Fv-1 locus. To determine if different Fv-1n strains of mice were equally susceptible to virus-induced neurological disease, we inoculated NFS, C3H, DBA/2, CBA, AKR, C58, and NZB mice at birth with Cas-Br-M murine leukemia virus and observed them for the development of tremor and hind-limb paralysis. Three patterns of disease were observed: NFS and C3H mice developed disease within 3 months postinoculation; DBA/2 and CBA mice became affected between 8 and 15 months postinoculation; and no disease was observed in AKR, C58, or NZB mice up to 15 months after infection with Cas-Br-M murine leukemia virus. Studies of genetic crosses between intermediate-latency (DBA/2) or long-latency (AKR) strains with short-latency (NFS) strains showed that intermediate latency and long latency were semidominant traits determined by two or more interacting but independently assorting loci. These genes appear to determine the rate at which the virus replicates and at which viral gene products accumulate in the central nervous system.
Hoffman
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D000483:Alleles; D000818:Animals; D001921:Brain / Q000382:microbiology; D003433:Crosses, Genetic; D004261:DNA Replication; D005260:Female; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity*; D007942:Leukemia, Experimental / Q000382:microbiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009422:Nervous System Diseases / Q000235:genetics / Q000382:microbiology*; D011247:Pregnancy; D013045:Species Specificity; D013154:Spleen / Q000382:microbiology; D014779:Virus Replication