Back to Search
Start Over
Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model.
- Source :
-
Neuron [Neuron] 2008 Nov 26; Vol. 60 (4), pp. 598-609. - Publication Year :
- 2008
-
Abstract
- A familial form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 prion protein (PrP) mutation. Tg(CJD) mice expressing the mouse homolog of this mutant PrP synthesize a misfolded form of the mutant protein, which is aggregated and protease resistant. These mice develop clinical and pathological features reminiscent of CJD, including motor dysfunction, memory impairment, cerebral PrP deposition, and gliosis. Tg(CJD) mice also display electroencephalographic abnormalities and severe alterations of sleep-wake patterns strikingly similar to those seen in a human patient carrying the D178N/V129 mutation. Neurons in these mice show swelling of the endoplasmic reticulum (ER) with intracellular retention of mutant PrP, suggesting that ER dysfunction could contribute to the pathology. These results establish a transgenic animal model of a genetic prion disease recapitulating cognitive, motor, and neurophysiological abnormalities of the human disorder. Tg(CJD) mice have the potential for giving greater insight into the spectrum of neuronal dysfunction in prion diseases.
- Subjects :
- Animals
Brain pathology
Brain physiopathology
Cerebral Cortex metabolism
Cerebral Cortex pathology
Cerebral Cortex physiopathology
Creutzfeldt-Jakob Syndrome genetics
Creutzfeldt-Jakob Syndrome physiopathology
Disease Models, Animal
Electroencephalography
Endoplasmic Reticulum metabolism
Endoplasmic Reticulum pathology
Energy Metabolism genetics
Evoked Potentials genetics
Memory Disorders metabolism
Memory Disorders physiopathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Movement Disorders metabolism
Movement Disorders physiopathology
Mutation genetics
Sleep Wake Disorders metabolism
Sleep Wake Disorders physiopathology
Brain metabolism
Creutzfeldt-Jakob Syndrome complications
Memory Disorders genetics
Movement Disorders genetics
Prions genetics
Sleep Wake Disorders genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 60
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 19038218
- Full Text :
- https://doi.org/10.1016/j.neuron.2008.09.008