Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent.
To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using a 1 kb hamster cDNA clone containing the 0.76 kb HPrP open reading frame under control of the neuron-specific enolase promoter. In these mice, expression of HPrP was detected only in brain tissue, with highest levels found in neurons of the cerebellum, hippocampus, thalamus, and cerebral cortex. These transgenic mice were susceptible to infection by the 263K strain of hamster scrapie with an average incubation period of 93 days, compared to 72 days in normal hamsters. In contrast, nontransgenic mice were not susceptible to this agent. These results indicate that neuron-specific expression of the 1 kb HPrP minigene including the HPrP open-reading frame is sufficient to mediate susceptibility to hamster scrapie, and that HPrP expression in nonneuronal brain cells is not necessary to overcome the TSE species barrier.
Race
R E
RE
Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
Priola
S A
SA
Bessen
R A
RA
Ernst
D
D
Dockter
J
J
Rall
G F
GF
Mucke
L
L
Chesebro
B
B
Oldstone
M B
MB
D000818:Animals; D001483:Base Sequence; D002531:Cerebellum / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D006224:Cricetinae; D004247:DNA / Q000737:chemistry; D018891:Dentate Gyrus / Q000737:chemistry; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D011328:Prions / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012608:Scrapie / Q000235:genetics; D013788:Thalamus / Q000737:chemistry
D011328:Prions; D012333:RNA, Messenger; D004247:DNA