Neurological illness in transgenic mice expressing a prion protein with an insertional mutation

Roberto Chiesa, Pedro Piccardo, Bernardino Ghetti, David A. Harris

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Familial prion diseases are caused by mutations in the gene encoding the prion protein (PrP). We have produced transgenic mice that express the mouse homolog of a mutant human PrP containing a nine octapeptide insertion associated with prion dementia. These mice exhibit a slowly progressive neurological disorder characterized clinically by ataxia and neuropathologically by cerebellar atrophy and granule cell loss, gliosis, and PrP deposition that is most prominent in the cerebellum and hippocampus. Mutant PrP molecules expressed in the brains of these mice are resistant to digestion by low concentrations of proteinase K and display several other biochemical properties reminiscent of PrP(Sc,) the pathogenic isoform of PrP. These results establish a new transgenic animal model of an inherited human prion disorder.

Original languageEnglish
Pages (from-to)1339-1351
Number of pages13
JournalNeuron
Volume21
Issue number6
DOIs
StatePublished - Dec 1998

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Transgenic Mice
Mutation
Endopeptidase K
Cerebellar Ataxia
Genetically Modified Animals
Prion Diseases
Gliosis
Prions
Mutant Proteins
Nervous System Diseases
Cerebellum
Atrophy
Prion Proteins
Digestion
Hippocampus
Protein Isoforms
Animal Models
Brain
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. / Chiesa, Roberto; Piccardo, Pedro; Ghetti, Bernardino; Harris, David A.

In: Neuron, Vol. 21, No. 6, 12.1998, p. 1339-1351.

Research output: Contribution to journalArticle

Chiesa, Roberto ; Piccardo, Pedro ; Ghetti, Bernardino ; Harris, David A. / Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. In: Neuron. 1998 ; Vol. 21, No. 6. pp. 1339-1351.
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