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From: TSS (216-119-143-165.ipset23.wt.net)
Subject: Differences in Scrapie-Induced Pathology of the Retina and Brain...
Date: December 3, 2004 at 8:10 am PST

-------- Original Message --------
Subject: 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
Date: Fri, 3 Dec 2004 10:14:52 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE


##################### Bovine Spongiform Encephalopathy #####################

(American Journal of Pathology. 2004;165:2055-2067.)
© 2004 American Society for Investigative Pathology

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

Lisa Kercher*, Cynthia Favara*, Chi-Chao Chan{dagger} , Richard Race*
and Bruce Chesebro*

From the Laboratory of Persistent Viral Diseases,* Rocky Mountain
Laboratories, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Hamilton, Montana; and the Laboratory of
Immunology,{dagger} National Eye Institute, National Institutes of
Health, Bethesda, Maryland

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 (PrP-res) were detected in retina and brain
before clinical onset. Retinal PrP-res 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 PrP-res 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 PrP-res production in multiple cell
types was required to produce retinal degeneration, whereas in brain
PrP-res production by neurons or astrocytes alone was sufficient to
cause neuronal damage via direct or indirect mechanisms.

http://ajp.amjpathol.org/cgi/content/abstract/165/6/2055

TSS

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