Spontaneous neurodegeneration in transgenic mice with mutant prion protein.
Transgenic mice were created to assess genetic linkage between Gerstmann-Sträussler-Scheinker syndrome and a leucine substitution at codon 102 of the human prion protein gene. Spontaneous neurologic disease with spongiform degeneration and gliosis similar to that in mouse scrapie developed at a mean age of 166 days in 35 mice expressing mouse prion protein with the leucine substitution. Thus, many of the clinical and pathological features of Gerstmann-Sträussler-Scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution, illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals.
Hsiao
K K
KK
Department of Neurology, University of California, San Francisco 94143.
Scott
M
M
Foster
D
D
Groth
D F
DF
DeArmond
S J
SJ
Prusiner
S B
SB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D003062:Codon; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D019286:Endopeptidase K; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D007930:Leucine; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D018620:PrPSc Proteins; D011328:Prions / Q000235:genetics*; D012697:Serine Endopeptidases / Q000378:metabolism; D014162:Transfection; D014617:Vacuoles / Q000473:pathology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D003062:Codon; D018620:PrPSc Proteins; D011328:Prions; D014764:Viral Proteins; D004247:DNA; D012697:Serine Endopeptidases; D019286:Endopeptidase K; D007930:Leucine