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Starting from the (C57BL/6 x DBA/2)F1 generation (Fv-2s/Fv-2r), 16 serial backcrosses to mice of the parental DBA/2 strain (Fv-2s/Fv-2s) were bred. In each generation, heterozygous Fv-2s/Fv-2r segregants were selected and backcrossed with a DBA/2 parent. In the 16th generation, Fv-2s/Fv-2r heterozygotes were intercrossed, and Fv-2r/Fv-2r homozygotes were selected for interbreeding to establish a congenic strain, D2.B6-Fv-2r. The successful establishment of this congenic strain is in contrast with previous findings suggesting that homozygosity for the Fv-2r allele might be a lethal genotype on the DBA/2 genetic background. At least 10 centimorgans of Fv-2r-linked chromosomal material originating from the C57BL/6 ancestor remains in the D2.B6-Fv-2r genome, as shown by the continued presence of C57BL/6 alleles at the flanking Kfo-1 and Bgl-s loci. The observed recombination frequency for the intervals between Fv-2 and Bgl-s was 6.8%.

To determine the mechanism by which the recessive Fv-2r gene confers complete resistance to spleen focus formation and to the induction of early splenomegaly characteristic of the Friend virus (FV) disease syndrome, we compared the parameters of FV infection in susceptible DBA/2 (D2) (Fv-1n, Fv-2s) and partially congenic D2.Fv-2r (Fv-1n, Fv-2r) mice. After infecting these mice with N-tropic FV complex, we followed the replication of spleen focus-forming virus (SFFV) and the generation of SFFV-transformed tumor colony-forming cells (CFC) in their spleens. By both parameters D2.Fv-2r mice were 20- to 100-fold less susceptible than DBA/2 controls, but the inhibition was only partial. Transplantation of washed spleen cells from SFFV-infected DBA/2 mice resulted in equal growth and recovery of tumor CFC from both D2.Fv-2r and Fv-2s mice. However, these tumor cells grew as colonies in Fv-2s mice, whereas they grew diffusely in the spleens of D2.Fv-2r hosts and did not develop into macroscopically or microscopically visible colonies. Thus the completeness of the resistance to spleen focus formation that defines the Fv-2r gene was reflected only in the complete suppression of the colonial growth of tumor cells, whereas the other parameters of infection showed no or only partial inhibition.

From the (C57BL/6 X DBA/2)F1 cross, 13 serial backcrosses to the DBA/2 parental mouse strain were bred with selection by progeny testing in each generation for the Fv-2s/Fv-2r heterozygous genotype. Intercrossing heterozygotes of the 13th backcross generation produced no Fv-2r/Fv-2r homozygotes. Homozygosity for the Fv-2r allele thus appeared to be lethal on a DBA/2 background and in the absence of protector gene(s) of the C57BL strain.