Table 5.
Inhibition of scrapie disease development by repression of Prnp gene expression in transgenic mice
| Recipient | Treatment | Inoculum | CNS dysfunction | Incubation time (mean days ± SEM) |
|---|---|---|---|---|
| FVB | —* | RML | 11/11 | 122 ± 3 |
| Tg(tTA:PrP)3 | —* | RML | 4/4† | 51 ± 0 |
| Tg(tTA:PrP)3 | − Dox‡ | — | 0/6 | >200 |
| Tg(tTA:PrP)3 | + Dox§ | RML | 0/7 | >380 (n = 5)¶ |
| Non Tg(tTA:PrP)3‖ | —* | RML | 0/10 | >380 (n = 8)¶ |
| Tg(tetO-PrP/E6740) | —* | RML | 0/8 | >380 (n = 6)¶ |
| Prnp0/0 | —* | — | 0/10 | >380 |
Animals from these groups were kept at all times without doxycycline.
Animals in this category first presented with ataxia at 51 days postinoculation and with additional signs of neurologic dysfunction at 69 days. Traditionally, the diagnosis of experimental scrapie in mice requires two signs of neurologic dysfunction as described (32).
Animals were born from parents maintained on doxycycline in the drinking water. Treatment was ceased at 3 weeks of age.
Doxycycline was administered in the drinking water (2 mg/ml) 1 week before inoculation.
Two animals from each of these groups were sacrificed for histopathology at 200 days postinoculation.
Animals in this group did not harbor any transgene.