Table 1.
Comparison of different TSE agents in mice with WT PrP
| Country–origin (no. of species before mouse) | Diagnosis | Agent name | Mouse incubations CD-1 (Tga20) ≥passage 2 | Mouse brain pathology | Mouse brain PrP-res | |
|---|---|---|---|---|---|---|
| 1 | U.S.–human (++) | sCJD | SY-CJD | 370 (307) days | Restricted | Type 1 |
| 2 | Italy–human (+) | sCJD | LU-CJD | 380 (324) days | Restricted | Type 1 |
| 3 | U.K.–human | GSS | MA-CJD | 380 (350) days | Restricted | Type 1 |
| 4 | Japan–human (+) | GSS | FU-CJD | 120 (70) days | Widespread + amyloid | Type 1 |
| 5 | Japan–human | GSS | YAM-CJD | 130 days | Widespread + amyloid | Type 1 |
| 6 | U.K.–human | vCJD | vCJD | 185 (126) days | BSE pattern + amyloid | Type 2 |
| 7 | U.K.–cow | BSE | BSE | 160 days | BSE pattern + amyloid | Type 2 |
| 8 | kuru–human (+) | kuru | kCJD | 440 (154) days | kCJD specific | Type 1 |
| 9 | U.K.–sheep | Scrapie | 22L-sc | 140 (87) days | Scrapie variant | Type 1 |
| 10 | U.K.–sheep | Scrapie | Ch (RML)-sc | 120 days | Scrapie variant | Type 1 |
| 11 | U.K.–sheep (++++) | Scrapie | 263K-Sc | 330 (310) days | 263K specific | Type 1 |
Key features of transmissible spongiform encephalopathy (TSE) agents propagated in mice with country of origin, original species, and disease diagnosis. The agent name indicates the host from which it was isolated, e.g., CJD for human. Sporadic Creutzfeldt–Jakob disease (sCJD) causes a rapidly progressive dementia globally in older people. In Gerstmann–Sträussler–Sheinker disease (GSS), patients with a 102L prion protein (PrP) mutation have symptoms for ≈5 years with cerebellar PrP amyloid plaques. A plus sign (+) indicates prior nonmurine species passages. SY-CJD was first passaged in guinea pigs and hamsters (++) (6). LU-CJD was passaged in hamsters (+), whereas MA-CJD brain homogenate was inoculated directly in mice. The Japanese GSS-102L PrP samples yield short mouse incubations and widespread brain lesions with the same PrP-res band pattern as sCJD (11,12), and FU-CJD was first passaged in rats. The human variant CJD (vCJD) and cow bovine spongiform encephalopathy (BSE) isolates produce type 2 PrP-res (Fig. 2) and a unique BSE lesion profile (11). Mutant 263K-sc was cloned at limiting dilution in 5 different species and then again selected for low mouse pathogenicity [>600 versus 65 days in hamsters (15)]. When retransmitted to mice, its biological properties were changed profoundly, but PrP-res remained type 1 (11). All mice were inoculated with 1% brain homogenates as detailed in refs. 5 and 6 and SI Methods.