Structure and Function of the PrP Gene

After the disruption and successful rescue by complementation of the PrP gene, many research efforts have concentrated on defining cis-elements of the PrP gene that are sufficient to support prion pathogenesis and propagation in PrP null mice. Transgenics have facilitated 

This ataxic defect observed in three separate transgenic lines was completely abolished by introducing one or more copies of a wild-type murine PrP gene into mice carrying multiple copies of the truncated PrP gene. The possibility that expression of wild-type PrP could in some way prevent expression of the truncated molecules was ruled out because Western blots of brain extracts showed the same level of truncated PrP in the rescued as in the truncated PrP-expressing mice. 

When comparing these studies with others, it is worth mentioning that the truncated transgenes of both Fischer et al, (1996) and Shmerling et al., (1998) were based on a xmni-Pmp gene, which has been demonstrated to lack expression in Purkinje cells. 

Before the availability of Nuclear Magnetic Resonance (NMR) data revealing three a helices in a recombinant PrP (Riek et al., 1997), Muramoto et al. (1997) used a four-helix-bundle model of PrP (Huang et al, 1994) to construct proteins with each of the predicted helical regions deleted. The aim was to assess the role of each region of the putative secondary structure, as well as those adjacent and intervening 

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