Table 3.
Comparison of the Results of the Transmission Studies of Various Human Prions between Different Genetically Modified Mice
| Transgene | ChM | MHu2M | MHu2M (M165V, E167Q) | HuPrP-129M | HuPrP-129V | |||||||||
| Codon 129 | Met | Met | Met | Met | Val | |||||||||
| Tg mice | KiChM | Tg(MHu2M) 5378/Prnp0/0 | Tg(MHu2M, M165V, E167Q) 22372/Prnp0/0 | Tg (HuPrP129M Prnp0/0)−35 | Tg(HuPrP,M129) 440/Prnp0/0 | Tg (HuPrP,V129)152/Prnp0/0 | ||||||||
| Expression level | 1 × Mo | 1 × Hu | 1∼2 × Hu | 2 × Hu | 2 × Hu | 2 × Hu | 4–8 × Hu | |||||||
| References | Present paper | Korth et al 13 | Korth et al 13 | Asante et al 12 | Korth et al 13 | Hill et al 9 | Korth et al 13 | |||||||
| Incubation Times* | ||||||||||||||
| sCJD-MM1 | 134–153 | 180–217 | 106–114 | 223–237* | 155–165 | 210±4 | 254±6 | |||||||
| -MM2 | >650, >680 | 232 ± 5, >580 | 368–556 | |||||||||||
| -MM2-T | 539, 558 | 221 ± 6 | 303 ± 20 | 699 ± 30 | ||||||||||
| -MV1 | 141 ± 5 | 214–215 | 124 ± 3 | 241 ± 1§ | 176 ± 2 | |||||||||
| -MV2 | >640 | >450 | 437 ± 31§ | 307–419 | 209–231 | |||||||||
| -VV2 | >750 | 433−531 | >450 | 354§ | 248–448 | 195–223 | ||||||||
| vCJD | >700 | 563–647 | 335–380 | 340–720 | 228 ± 15 | |||||||||
| Susceptibility¶ | ||||||||||||||
| Susceptible | sCJD-MM1 | sCJD-MM1 | sCJD-MM1 | sCJD-MM1*§ | sCJD-MM1 | sCJD-MM1§ | sCJD-MM1 | |||||||
| -MV1 | -MM2-T | -MV1 | -MV1 | -VV2 | -MM2 | |||||||||
| np-dCJD | vCJD | -MV2 | -MV2 | |||||||||||
| CJD232 | -MM2 | -VV2 | ||||||||||||
| GSS101 | ||||||||||||||
| Less susceptible | sCJD-MM2-T | sCJD-VV2 | sCJD-VV2 | sCJD-MV2*§ | sCJD-MM2-T | vCJD | ||||||||
| vCJD | vCJD | -MM2-T | -VV2§ | -VV2 | ||||||||||
| vCJD | vCJD | |||||||||||||
| Resistant | sCJD-VV2 | sCJD-MM2 | sCJD-MV2 | sCJD-MM2 | ||||||||||
| p-dCJD | -MV2 | |||||||||||||
| -VV2 | ||||||||||||||
| End-point titration for MM1-sCJD‡ | ||||||||||||||
| LogLD50/g | 7.8 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | |||||||
| For sCJD-MM1 | (case,H-3) | |||||||||||||
| PrPres size through the first passage† | ||||||||||||||
| sCJD-MM1 | ∼21 kDa | ∼21 kDa | ∼21 kDa | ∼21 kDa | N.D. | Some, shifted | N.D. | |||||||
| -MM2-T | ∼19 kDa | ∼19 kDa | N.D. | N.D. | N.D. | |||||||||
| vCJD | ∼20 kDa | ∼ 19 kDa | ∼19 kDa | ∼19 kDa | N.D. | Shifted | N.D. | |||||||
N.D.; not described.
*Incubation times; the mean (and the standard deviation or standard error of mean if available) of the days from the inoculation to the development of illness. For comparison between different genetically modified mice, results for sporadic CJD cases have been cited.
†PrPres sizes through the first passages; the mobility on SDS-PAGE of the PrPres derived from the mice inoculated with the indicated human prions.
‡End-point titration for sCJD-MM1; this was calculated according to Behrens-Karber’s method based on the results of the transmission studies using serially-diluted brain homogenates.
§Because the classification of human prion diseases are different, their type-1 and type-2 PrPres were interpreted as our PrPres type 1, and their type 3 as our PrPres type 2.
¶Susceptible, all mice inoculated developed clinical prion diseases; less susceptible, some of the mice inoculated lacked either clinical or pathological sign of prion disease; resistant, none of the mice had any sign of prion disease.