FIGURE 3.

Sporadic CJD PrP^Sc has PrP genotype and brain region-specific requirements for in vitro conversion activity. A, protease-pretreated sporadic CJD PrP^Sc (T1MM, T2MM, T3MM, and T3VV) used to generate PrP^res from a PrP^C substrate enriched for the gray (Gr) or white (Wh) matter regions (RG) of brain tissue with a PrP codon 129 genotype (GT) either MM, MV, or VV. Conversion activity is the -fold increase in PrP^res for each incubated sample over its corresponding control frozen sample. The dotted line indicates no conversion activity. Significance (*, p < 0.05; **, p < 0.01) was calculated relative to the mean conversion activity detected in the presence of a mouse brain homogenate using one-way analysis of variance with Dunnett's Multiple Comparison Test. B, conversion activity of individual sources of T1MM (n = 3), T2MM (n = 3), and T3MM (n = 2) sporadic CJD PrP^Sc using PrP^C substrate from gray and white matter of the methionine homozygous donors. C, ability of PrP^C substrates with different codon 129 genotypes and derived from different brain regions to support PrP^res formation by any sporadic CJD subtype. D, ability of methionine homozygous PrP^C substrates derived from the gray and white matter of two different donors, to support the conversion activity of T1MM and T2MM PrP^Sc. E, conversion activity of gray and white matter-enriched methionine homozygous substrates seeded with T1MM and T2MM sporadic CJD PrP^Sc. Error bars, S.E.