STUDIES OF GENETIC TRANSMISSION OF MURINE LEUKEMIA VIRUS BY AKR MICE : I. CROSSES WITHFv-1n STRAINS OF MICE

AKR mice, which regularly contain infectious murine leukemia virus, were mated with four Fv-1n strains of mice which show little or no expression of virus. F1, F2, and first and second backcross generation hybrids were tested for virus in tail tissue at 2 and 6 wk of age. The segregation data indicate that the AKR mouse contains two unlinked, autosomal, chromosomal loci, either of which suffices to induce detectable levels of infectious virus in Fv-1n progeny by 6 wk of age. One of the loci (tentatively referred to as V1) is on linkage group I, 25–30 map units from the locus for albino; the gene order tentatively appears to be N1-c-Hbb

QUANTITATIVE STUDIES OF NATURALLY OCCURRING MURINE LEUKEMIA VIRUS INFECTION OF AKR MICE

Quantitative studies were made of the organ distribution of murine leukemia virus in AKR mice of various ages. Infectious virus first appeared shortly before or after birth and was continuously present in all mice thereafter. Highest infectivity titers were found in uterus and bone, with spleen slightly lower. Virus titers in normal thymus were relatively low, but increased significantly with the development of thymic lymphoma. The level of viremia decreased after the 1st month of life, but increased sharply in lymphomatous mice

STUDIES OF GENETIC TRANSMISSION OF MURINE LEUKEMIA VIRUS BY AKR MICE : II. CROSSES WITHFv-1b STRAINS OF MICE

The transmission of murine leukemia virus (MLV) to hybrids between AKR and Fv-1b mice was studied in order to evaluate the effect of the Fv-1 gene on endogenous MLV infection and to attempt to determine if the genetic loci contributed by AKR carry viral genetic determinants. Fv-1 was shown to have a marked suppressive effect on time of appearance of detectable infectious virus and on the titers attained in vivo, but did not affect the ability of the cells to produce virus in vitro after induction with 5-iododeoxyuridine. The host range type of the virus detected in the hybrid mice was almost always of the type carried by AKR, although the low-virus Fv-1b parents carry the genome of a different host range type. This finding provides strong, but not conclusive, evidence that the virus-inducing loci of AKR contain MLV genetic determinants

A MAJOR GENETIC LOCUS AFFECTING RESISTANCE TO INFECTION WITH MURINE LEUKEMIA VIRUSES : II. APPARENT IDENTITY TO A MAJOR LOCUS DESCRIBED FOR RESISTANCE TO FRIEND MURINE LEUKEMIA VIRUS

The N-B locus affecting tissue culture infectivity with naturally occurring murine leukemia viruses appears to be identical to the Fv-1 locus described for sensitivity to Friend leukemia virus. Results of tissue culture studies were parallel to results of studies in vivo and indicate that the F-S virus is N-tropic and the F-B virus is NB-tropic. Inbred and partially congenic mouse strains sensitive at Fv-1 show N-type sensitivity; strains resistant at Fv-1 show B-type sensitivity. The Fv-2 locus does not appear to exert significant effect in tissue culture. Knowledge of N-B type has been useful in predicting Fv-1 sensitivity

A MAJOR GENETIC LOCUS AFFECTING RESISTANCE TO INFECTION WITH MURINE LEUKEMIA VIRUSES : I. TISSUE CULTURE STUDIES OF NATURALLY OCCURRING VIRUSES

Previous studies have indicated that all naturally occurring murine leukemia viruses propagate significantly more efficiently on embryo cells of either NIH Swiss or BALB/c mice. Studies of the plaquing efficiency of representative viruses on embryo cells of various inbred and hybrid mice indicate that the pattern of sensitivity of the cells is genetically determined. All of 23 strains tested were found to resemble either NIH Swiss (N-type) or BALB/c (B-type) with respect to plaquing efficiency of these viruses. Virus growth on embryo cells derived from (N-type x B-type)F1 hybrids indicated dominance of resistance to both types of viruses. Backcross hybrid studies indicated that a single locus is the primary determinant of the host-range patterns observed. This locus has no effect on growth of certain laboratory-passaged leukemia viruses which propagate equally well on embryo cells of all mouse strains, F1, and backcross hybrids. Though other genetic and nongenetic factors influence viral growth or expression in vitro and in vivo, the genetic locus described appears of major significance in the biology of murine leukemia