NR AKIK
AU Sakaguchi,S.; Katamine,S.; Nishida,N.; Moriuchi,R.; Shigematsu,K.; Sugimoto,T.; Nakatani,A.; Kataoka,Y.; Houtani,T.; Shirabe,S.; Okada,H.; Hasegawa,S.; Miyamoto,T.; Noda,T.
TI Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene
QU Nature 1996 Apr 11; 380(6574): 528-31
PT journal article
AB Prion protein (PrP) is a glycoprotein constitutively expressed on the neuronal cell surface. A protease-resistant isoform of prion protein is implicated in the pathogenesis of a series of transmissible spongiform encephalopathies. We have developed a line of mice homozygous for a disrupted PrP gene in which the whole PrP-coding sequence is replaced by a drug-resistant gene. In keeping with previous results, we find that homozygous loss of the PrP gene has no deleterious effect on the development of these mice and renders them resistant to prion. The PrP-null mice grew normally after birth, but at about 70 weeks of age all began to show progressive symptoms of ataxia. Impaired motor coordination in these ataxic mice was evident in a rotorod test. Pathological examination revealed an extensive loss of Purkinje cells in the vast majority of cerebellar folia, suggesting that PrP plays a role in the long-term survival of Purkinje neurons.
IN Die Autoren erzeugten eine Mauslinie, bei der die kodierende Region des Prionproteins durch ein Resistenzgen ersetzt wurde. Die Mäuse wurden dadurch Scrapie-resistent, ohne zunächst offensichtliche Defekte zu zeigen. Nach 70 Wochen jedoch, entwickelten sie alle zunehmende Ataxien. Pathologisch wurde ein umfangreicher Verlust von Purkinjezellen gefunden.
MH Animal; Ataxia/genetics; Brain/pathology; *Cell Death; Drug Resistance/genetics; Glutamate Decarboxylase/metabolism; Heterozygote; *Homozygote; Mice; Mutagenesis; Prion Diseases/genetics; Prions/*genetics; Purkinje Cells/*pathology; Support, Non-U.S. Gov't
AD Department of Bacteriology, Nagasaki University School of Medicine, Nagasaki, Japan.
SP englisch
PO England
OR Prion-Krankheiten 7