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.

Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model / S. Dossena, L. Imeri, M. Mangieri, A. Garofoli, L.L. Ferrari, A. Senatore, E. Restelli, C. Balducci, F. Fiordaliso, M. Salio, S.E.F. Bianchi, L. Fioriti, M. Morbin, A. Pincherle, G. Marcon, F. Villani, M. Carli, F. Tagliavini, G. Forloni, R. Chiesa. - In: NEURON. - ISSN 0896-6273. - 60:4(2008 Nov 26), pp. 598-609.

Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model

L. Imeri
Secondo
;
L.L. Ferrari;S.E.F. Bianchi;
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.
CELLBIO; HUMDISEASE; SYSNEURO
Settore BIO/09 - Fisiologia
26-nov-2008
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/46828
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