title: A 2-year longitudinal study of swimming navigation in mice devoid of the prion protein: no evidence for neurological anomalies or spatial learning impairments.
abstract: Uncontrolled accumulation of a conformationally distorted protein (PrP(Sc)) is supposed to be the pathological process leading to spongiform encephalopathy. Targeted disruptions of the Prn-P gene in the mouse have resulted in animals that did not show anomalies in spatial and avoidance learning and were resistant to experimental infections. However, another Prn-P knockout mouse was reported to show ataxia and Purkinje cell degeneration developing after 70 weeks of age. In this study the initial observations are confirmed on swimming navigation of PrP-null mutant mice using an enlarged sample of 58 mice. A representative subsample of 16 mice was then followed up for their ability of swimming navigation up to an age of two years (104 weeks). Surviving PrP-null mutants (n = 4) and controls (n = 6) did not differ in any measure, nor were there indications of ataxia and Purkinje cell degeneration. It was concluded that the PrP-knockout mice used by Büeler et al. were probably normal with respect to aging processes and that resistance to scrapie is not necessarily paid for by late neuronal degeneration. The reasons for the discrepancy between different knockout experiments require experimental clarification, however.
authors.affiliation: Institute of Anatomy, University of Zürich-Irchel, Zürich, Switzerland. hplipp@anatomie.unizh.ch
authors.forename: H P
authors.initials: HP
authors.lastname: Lipp
authors.forename: M
authors.initials: M
authors.lastname: Stagliar-Bozicevic
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: D P
authors.initials: DP
authors.lastname: Wolfer
mesh_terms: D000818:Animals; D005260:Female; D008137:Longitudinal Studies; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics; D009949:Orientation / Q000502:physiology*; D011328:Prions / Q000235:genetics*; D011689:Purkinje Cells / Q000502:physiology; D013028:Space Perception / Q000502:physiology*; D013550:Swimming / Q000502:physiology
chemical_list: D011328:Prions