presentazione tratta dal sito del Centre for clinical Brain Science (http://www.ccbs.ed.ac.uk/default.asp) sulla malattia prionica e sul modello murino transgenico.

5. Prion Protein: Western Blot

6. Prion Protein Gene ( PRNP ) M129V 1 254

7. Codon 129 Genotype & CJD sCJD: Alperovitch, et al . (1999) Lancet, 353, 1673-4 iCJD: Brown, P. et al . (2000) Neurology, 55, 1075-81 UK Pop: Nurmi, M. H., Bishop, M., et al . (2003) Acta Neurol Scand, 108, 374-378 Sporadic CJD (n=832) Variant CJD (n=146) Iatrogenic CJD (n=128) MM 71% 100% 57% MV 13% 0% 20% VV 16% 0% 23% Normal Pop (n=406) 40% 48% 11% UK

10. Human prion protein transgene (Codon 129: M or V) Mouse prion gene replaced by transgene HuMM HuVV (HuMV) Wild-type - HuMM - HuMV - HuVV - ‘ Human’ Transgenic Mice

11. Variant CJD (MM) Transmission Codon 129 Affecting ‘Susceptibility’ Bishop et al Lancet Neurology 2006; 5 (5): p.393-398 Overall Score ------ Mice Positive For: CLINICAL TSE TSE VACUOLATION ABNORMAL PrP ------ BSE Inoculation 1/15 ------ x0 x1 x1 ------ 0/22 11/15 ------ x1 x1 x11 ------ 0/23 12/16 ------ x2 x6 x12 ------ 0/18 HuVV HuMV HuMM

12. Variant CJD (MM) vs. Blood Transfusion vCJD Bishop et al Lancet Neurology 2006; 5 (5): p.393-398 Bishop, et al (2008) PLoS ONE, 3, e2878 Overall Score ------ Mice Positive For: CLINICAL TSE TSE VACUOLATION ABNORMAL PrP 1/15 1/17 ------ x0 x0 x1 x0 x1 x1 11/15 8/17 ------ x1 x2 x1 x0 x11 x8 12/16 13/14 ------ x2 x1 x6 x8 x12 x13 HuVV HuMV HuMM

13. HuMM – 700 days HuMM – 500 days HuMV – 700 days HuMV – 600 days Variant CJD (MM) Inoculation Codon 129 Affecting Progression of PrP Deposition

14. Sporadic CJD Inoculation Six typical cases of sCJD defined by codon 129 and PrP Sc type: MM1 & MM2 MV1 & MV2 VV1 & VV2 HuMM HuMV HuVV Analysis Incubation period to clinical TSE TSE vacuolation scoring PrP Sc typing by Western blot PrP Sc detection by immunocytochemistry Intra-cerebral