Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted Prp gene

被引:395
作者
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
机构
[1] NAGASAKI UNIV,SCH MED,DEPT BACTERIOL,NAGASAKI 852,JAPAN
[2] NAGASAKI UNIV,SCH MED,DEPT PATHOL,NAGASAKI 852,JAPAN
[3] NAGASAKI UNIV,SCH MED,DEPT PHARMACOL,NAGASAKI 852,JAPAN
[4] NAGASAKI UNIV,SCH MED,DEPT INTERNAL MED 1,NAGASAKI 852,JAPAN
[5] KANSAI MED UNIV,DEPT ANAT,MORIGUCHI,OSAKA 570,JAPAN
[6] JAPANESE FDN CANC RES,INST CANC,DEPT CELL BIOL,TOKYO 170,JAPAN
关键词
D O I
10.1038/380528a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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(1). 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(2). In keeping with pre,ious results(3-8), 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(2). 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.
引用
收藏
页码:528 / 531
页数:4
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