Different behavior toward bovine spongiform encephalopathy infection of bovine prion protein transgenic mice with one extra repeat octapeptide insert mutation

In humans, insert mutations within the repetitive octapeptide region of the prion protein gene (Prnp) are often associated with familial spongiform encephalopathies. In this study, transgenic mice expressing bovine PrP (boTg mice) bearing an additional octapeptide insertion to the wild type (seven octapeptide repeats instead of six) showed an altered course of bovine spongiform encephalopathy (BSE) infection, reflected as reduced incubation times when compared with boTg mice expressing similar levels of the wild-type six-octapeptide protein. In both boTg mouse lines (bo60RTg and bo70RTg), incubation times were affected drastically depending on transgene expression levels and the inoculum used. In accordance with the lack of an interspecies barrier to BSE infection, we detected the typical signs of CNS spongiform degeneration by histopathological analysis and the presence of the bovine prion PrPres by Western blot or immunohistochemical analyses. When 70R-PrPres was propagated in bo70RTg mice, a similar earlier onset of clinical signs was observed compared with bo60RTg mice. Proteins PrP C and PrPres containing seven octapeptides (70R-PrP C and 70R-PrPres) showed similar protease sensitivity and insolubility in nondenaturing detergents to homologous 60R-PrPC and 60R-PrPres. In addition, bo70RTg mice showed a higher sensitivity than bo60RTg mice for detecting prion infection in specimens previously diagnosed as negative by conventional biochemical techniques. In the absence of clinical signs of disease, 70R-PrPres could be detected as early as 120 d after inoculation by immunohistochemical and Western blot analyses. These findings may help us improve the current mouse bioassays and understand the role of the octapeptide repeat region in susceptibility to disease.

Bibliographic Details

Main Authors:	Castilla, J., Gutiérrez Adán, Alfonso, Brun Torres, Alejandro, Pintado, B., Parra, B., Ramírez De Paz, Miguel Ángel, Salguero, F. J., Díaz San Segundo, F., Rábano, A., Cano, M. J., Torres Trillo, J. M.
Format:	artículo biblioteca
Language:	English
Published:	Society for Neuroscience 2004
Subjects:	BSE transmission, Transgenic mice, Prion, Octapeptide repeats, Bioassay, Scrapie, PrP,
Online Access:	http://hdl.handle.net/20.500.12792/5801 http://hdl.handle.net/10261/291373
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