PrP effects clarified

Lansbury and Caughey state in their Primer on prion proteins [1xSee all References[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 [2xNormal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Bueler, H, Fischer, M, Lang, Y, Bluethmann, H, Lipp, HP, DeArmond, SJ et al. Nature. 1992; 356: 577–582Crossref | PubMed | Scopus (1045)See all References[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. [3x129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. Manson, JC, Clarke, AR, Hooper, ML, Aitchinson, L, McConnell, I, and Hope, J. Mol Neurobiol. 1994; 8: 121–127Crossref | PubMed | Scopus (393)See all References[3].The phenomenon referred to by Lansbury and Caughey was observed only by Sakaguchi et al. [4xLoss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Sakaguchi, S, Katamine, S, Nishida, N, Moriuchi, R, Shigematsu, K, Sugimoto, T et al. Nature. 1996; 380: 528–531Crossref | PubMed | Scopus (380)See all References[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]xRescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein. Whittington, MA, Sidle, KCL, Gowland, I, Meads, J, Hill, AF, Pulman, MA et al. Nature Genet. 1995; 9: 197–201Crossref | PubMed | Scopus (119)See all References, [6]xPrP gene dosage and long term potentiation. Manson, JC, Hope, J, Clark, AR, Johnston, A, Black, C, and Macleod, N. Neurodegeneration. 1995; 4: 113–115Crossref | PubMedSee all References] for two different lines of PrP-null mice, ours and those of Manson et al., but these were not reflected in neurological deficits.