NR AYCV
AU Nazor,K.E.; Seward,T.; Telling,G.C.
TI Motor behavioral and neuropathological deficits in mice deficient for normal prion protein expression
QU Biochimica et Biophysica Acta - Molecular Basis of Disease 2007 Jun; 1772(6): 645-53
PT journal article; research support, n.i.h., extramural; research support, non-u.s. gov't
AB It has been difficult to reconcile the absence of pathology and apparently normal behavior of mice lacking prion protein (PrP), referred to as Prnp(0/0) mice, with a mechanism of prion pathogenesis involving progressive loss of PrPc-mediated neuroprotection. However, here we report that Prnp(0/0) mice exhibit significant age-related defects in motor coordination and balance compared with mice expressing wild type Prnp on a syngeneic background, and that the brains of behaviorally-impaired Prnp(0/0) mice display the cardinal neuropathological hallmarks of spongiform pathology and reactive astrocytic gliosis that normally accompany prion disease. Consistent with the appearance of cerebellar ataxia as an early symptom in patients with Gerstmann-Sträussler-Scheinker syndrome (GSS), an inherited form of human prion disease, motor coordination and balance defects manifested in a transgenic (Tg) mouse model of GSS considerably earlier than the onset of end-stage neurodegenerative disease. Our results are consistent with a mechanism in which loss of normal PrPc function is an important pathological component of prion diseases.
MH Animals; Behavior, Animal/physiology; Brain/metabolism/pathology/physiopathology; Female; Gene Expression; Gliosis/metabolism/pathology/physiopathology; Homozygote; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Transgenic; Motor Activity/genetics/*physiology; Mutation; Prion Diseases/genetics/pathology/*physiopathology; Prions/genetics/metabolism/*physiology; Time Factors
AD Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
SP englisch
PO Niederlande