Differences in pathogenicity among strains of the same or different avian leukosis virus subgroups.

An efficient induction of wasting disease in chickens by avian leukosis virus (ALV), particularly ALV subgroup C, requires >102 infectious units virus inoculated in mid embryogenesis. The most conspicuous symptoms of the disease were induced by ALV subgroup C; however, significant differences in the occurrence of wasting disease were found among individual members of this subgroup. Almost comparable pathogenicity was exhibited by ALV subgroup D, whereas viruses of subgroups B and A proved to be moderately and almost non-pathogenic, respectively. Using antibodies to cellular antigens, tissue alterations were shown clearly in ALV-C-infected chickens. An essential feature was depletion of lymphocytes in the thymus, bursa and spleen. While the number of dendritic cells in the bursa was increased, their representation in the thymus and spleen was reduced. In the spleen, however, the reduction of dendritic cells concerned only an ellipsoid compartment, which in itself was also markedly reduced. An increased number of macrophages in the thymus and spleen corresponded with the observed general activation of the monocyte-macrophage system. In the spleen, CD4+ T cells were reduced while CD8+ T cells were increased. In agreement with this finding was a failure of chickens to respond to Brucella antigen and an inability of their splenocytes to respond to Concanavalin A, both of which pointed to the damage of immune reactivity. Variation in the pathogenicity among individual ALV strains provides ground for depicting gene sequences playing an important role in ALV acute pathogenicity.

Opposite effects of modifiers of the ApcMin mutation in intestine and mammary gland.

Patterns of tumor susceptibility in different organs are widely divergent in mouse strains: one strain may be highly susceptible to tumors in one organ but resistant in another organ, whereas another strain may exhibit the opposite pattern (P. Demant, Semin. Cancer Biol., 3: 159-166, 1992). Therefore, susceptibility to tumors in different organs is assumed to be controlled by different sets of genes. On the other hand, many oncogenes and tumor suppressor genes are mutated in tumors from different organs, indicating that similar tumorigenic pathways operate in various tissues. To obtain insight into the interactions of susceptibility genes with one of such pathways, we compared tumorigenesis in intestine and mammary gland in recombinant congenic strains (RCSs) carrying the Apc(Min) mutation, affecting the Wnt pathway. The presence of Apc(Min) increased considerably the incidence of intestinal and mammary tumors. The individual RCSs differed in the number and latency of Apc(Min)-induced intestinal and mammary tumors and histological type of the latter. Unexpectedly, the strain distribution of susceptibility to the intestinal and mammary tumors in the Apc(Min)-bearing mice was opposite in the RCSs; the strains most susceptible for intestinal tumors were most resistant to mammary tumors and vice versa. This suggests that a set of genes controls the impact of the Apc(Min) mutation in both organs but with opposite effects. Elucidation of the basis of the observed strain differences in organ-specific Wnt pathway-mediated tumorigenesis will help to understand the interactions between germ-line encoded allelic differences in susceptibility genes and the spectrum of somatic mutations in tumor cells.