Effect of Q211 and K222 PRNP Polymorphic Variants in the Susceptibility of Goats to Oral Infection With Goat Bovine Spongiform Encephalopathy.
BACKGROUND
The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear.


METHODS
Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrP(Sc)) and prion infectivity by mouse bioassay.


RESULTS
R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrP(Sc) were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrP(Sc) accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44-45 months).


CONCLUSIONS
These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE.
Centro de Investigación en Sanidad Animal, Valdeolmos, Madrid, Spain.
Patricia
P
Aguilar-Calvo
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Südufer, Greifswald-InselRiems.
Christine
C
Fast
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Südufer, Greifswald-InselRiems.
Kerstin
K
Tauscher
Centro de Investigación en Sanidad Animal, Valdeolmos, Madrid, Spain.
Juan-Carlos
JC
Espinosa
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Südufer, Greifswald-InselRiems.
Martin H
MH
Groschup
Department of Pathology, University of Veterinary Medicine Hannover, Germany.
Muhammad
M
Nadeem
The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
Wilfred
W
Goldmann
Central Veterinary Institute, Wageningen UR, Lelystad, The Netherlands.
Jan
J
Langeveld
Central Veterinary Institute, Wageningen UR, Lelystad, The Netherlands.
Alex
A
Bossers
UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, France.
Olivier
O
Andreoletti
Centro de Investigación en Sanidad Animal, Valdeolmos, Madrid, Spain.
Juan-María
JM
Torres
D000818:Animals; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015511:Goat Diseases / Q000473:pathology* / Q000635:transmission*; D006041:Goats; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics*; D013045:Species Specificity
D011328:Prions
BSE; PRNP polymorphisms; goats; susceptibility/resistance; transgenic mice