Detection of PrPSc in lymphoid tissues of lambs experimentally exposed to the scrapie agent.

Histoblotting and immunohistochemistry were used to detect disease-associated prion protein (PrP(Sc)) in lymphoid tissues of lambs of known PrP genotype infected with the scrapie agent by stomach tube at the age of 2 months. The ileal and jejunal Peyer's patches and retropharyngeal and distal jejunal lymph nodes were studied 1 week, 5 weeks, 5 months and 11 months after inoculation. Other lymphoid tissues examined included superficial cervical lymph node, tonsil and spleen. PrP(Sc) was not detected in any tissue of any lamb at 1 week post-inoculation. At 5 weeks, PrP(Sc) was detected in tissues of lambs of susceptible PrP genotypes (AV(136)QQ(171) and VV(136)QQ(171)), but not lambs of other PrP genotypes (AA(136)QQ(171), AA(136)QR(171) and AV(136)QR(171)). PrP(Sc) was present in the germinal centres of tonsils, distal jejunal and retropharyngeal lymph nodes, and spleen. In the nodules of ileal and jejunal Peyer's patches, only occasional solitary cells showed the presence of PrP(Sc). At 5 months post-inoculation, increased accumulations of PrP(Sc) were detected in ileal and jejunal Peyer's patches, as well as in the retropharyngeal and distal jejunal lymph nodes of a single lamb inoculated with the agent from a sheep of the same susceptible PrP genotype. Eleven months after exposure to the scrapie agent, PrP(Sc) was detected in all lymphoid tissues examined from sheep of susceptible PrP genotypes. These studies show that PrP(Sc) was detectable in lymphoid tissues 5 weeks after exposure to the scrapie agent by stomach tube in lambs as young as 3 months of age and indicate that the PrP genotype is a significant factor for the rapid uptake and spread of the agent through lymphoid tissues.

Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs.

Canine hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) is a rare, naturally occurring inherited cancer syndrome observed in dogs. Genetic linkage analysis of an RCND-informative pedigree has identified a linkage group flanking RCND (CHP14-C05.377-C05.414-FH2383-C05. 771-[RCND-CPH18]-C02608-GLUT4-TP53-ZuBe Ca6-AHT141-FH2140-FH2594) thus localizing the disease to a small region of canine chromosome 5. The closest marker, C02608, is linked to RCND with a recombination fraction (theta) of 0.016, supported by a logarithm of odds score of 16.7. C02608 and the adjacent linked markers map to a region of the canine genome corresponding to portions of human chromosomes 1p and 17p. A combination of linkage analysis and direct sequencing eliminate several likely candidate genes, including tuberous sclerosis 1 and 2 genes (TSC1 and TSC2) and the tumor suppressor gene TP53. These data suggest that RCND may be caused by a previously unidentified tumor suppressor gene and highlight the potential for canine genetics in the study of human disease predisposition.