The Scripps Research Institute

Lansbury and Caughey state in their Primer on prion proteins [1] “Mice lacking the PrP gene, first produced by Charles Weissmann and colleagues, are viable, but have altered neuronal function and develop neurological abnormalities later in life.” This statement is misleading. The PrP-knockout mice produced in our laboratory [2] do not show neurological abnormalities at any time and we have never reported such an effect. Moreover, no structural neuronal abnormalities were found in an independent line of PrP-knockout mice generated by Manson et al. [3]. The phenomenon referred to by Lansbury and Caughey was observed only by Sakaguchi et al. [4] in a line of mice in which not only the PrP coding region but also part of the large intron was deleted. It is not possible to attribute the observed phenotype to ablation of PrP because correction of the phenotype through introduction of a PrP-expressing cDNA has not been carried out. Electrophysiological changes were reported [5,6] for two different lines of PrP-null mice, ours and those of Manson et al., but these were not reflected in neurological deficits.