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Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non‐transmissible, neurodegenerative disease and an expedited course of BSE infection
Author(s) -
Castilla J.,
Gutiérrez-Adán A.,
Brun A.,
Pintado B.,
Salguero F.J.,
Parra B.,
Segundo F. Díaz San,
Ramírez M.A.,
Rábano A.,
Cano M.J.,
Torres J.M.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.099
Subject(s) - bovine spongiform encephalopathy , genetically modified mouse , transgene , gliosis , biology , infectivity , virology , vacuolization , scrapie , microbiology and biotechnology , pathology , gene , disease , prion protein , medicine , virus , genetics , endocrinology , neuroscience
Transgenic (Tg) mice carrying four extra octapeptide repeats (OR) in the bovine PrP gene (10OR instead of 6) have been generated. In these mice, neuropathological changes were observed depending upon the level of transgene expression. These changes primarily involved a slowly advancing neurological disorder, characterized clinically by ataxia, and neuropathologically, by vacuolization in different brain areas, gliosis, and loss of cerebellar granule cells. Accumulation of insoluble bovine 10OR‐PrP (bo10OR‐PrP) was observed depending on the level of expression but no infectivity was found associated with this insoluble form. We also compared the behavior of bo6OR‐PrP and bo10OR‐PrP Tg mouse lines in response to BSE infection. BSE‐inoculated bo10ORTg mice showed an altered course of BSE infection, reflected by reduced incubation times when compared to bo6ORTg mice expressing similar levels of the wild type 6OR‐PrP. In BSE‐inoculated mice, it was possible to detect PrP res in 100% of the animals. While insoluble bo10OR‐PrP from non‐inoculated bo10ORTg mice was non‐infectious, brain homogenates from BSE‐inoculated bo10ORTg mice were highly infectious in all the Tg mouse lines tested. This Tg mouse model constitutes a new way of understanding the pathobiology of bovine transmissible spongiform encephalopathy. Its potential applications include the assessment of new therapies against prion diseases.