NR ARHX
AU Kercher,L.; Favara,C.; Chan,C.C.; Race,R.E.; Chesebro,B.
TI Differences in scrapie-induced pathology of the retina and brain in transgenic mice that express hamster prion protein in neurons, astrocytes, or multiple cell types
QU American Journal of Pathology 2004 Dec; 165(6): 2055-67
PT journal article
AB Prion protein (PrP) is expressed in many tissues and is required for susceptibility to scrapie and other prion diseases. To investigate the role of PrP expression in different cell types on pathology in retina and brain after scrapie infection, we examined transgenic mice expressing hamster PrP from the PrP promoter (tg7), the neuron-specific enolase promoter (tgNSE), or the astrocyte-specific glial fibrillary acidic protein promoter (tgGFAP). After intraocular inoculation with hamster scrapie, clinical disease developed in tg7 and tgNSE mice by 100 days and in tgGFAP mice by 350 days. Astrogliosis and scrapie-associated protease-resistant PrP (PrPres) were detected in retina and brain before clinical onset. Retinal PrPres was present in high amounts in both tg7 and tgNSE mice, however only tg7 mice developed retinal degeneration and extensive apoptosis. In contrast, in all three lines of mice high levels of brain PrPres accompanied by neurodegeneration were observed. Thus, PrP expression on neurons or astrocytes was sufficient for development of scrapie-induced degeneration in brain but not in retina. The combined effects of PrPres production in multiple cell types was required to produce retinal degeneration, whereas in brain PrPres production by neurons or astrocytes alone was sufficient to cause neuronal damage via direct or indirect mechanisms.
MH Animals; Apoptosis; Astrocytes/*metabolism/pathology; Brain Diseases/metabolism/*pathology; Comparative Study; Disease Susceptibility; Eye/pathology; Green Fluorescent Proteins/metabolism; Hamsters; In Situ Nick-End Labeling; Mice; Mice, Transgenic; Neurons/*metabolism/pathology; PrPsc Proteins/metabolism; Retinal Degeneration/metabolism/*pathology; Scrapie/metabolism/*pathology
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
SP englisch
PO USA