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Journal of Virology, November 2000, p. 10245-10248, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Identification of Upregulated Genes in
Scrapie-Infected Brain Tissue
Constanze
Riemer,
Ingo
Queck,
Dietrich
Simon,
Reinhard
Kurth, and
Michael
Baier*
Robert-Koch-Institut, 13353 Berlin, Germany
Received 4 May 2000/Accepted 2 August 2000
The pathogenesis of scrapie, and of neurodegenerative diseases in
general, is still insufficiently understood and is therefore being
intensely researched. There is abundant evidence that the activation of
glial cells precedes neurodegeneration and may thus play an important
role in disease development and progression. The identification of
genes with altered expression patterns in the diseased brain may
provide insight on the molecular level into the process which
ultimately leads to neuronal loss. Differentially expressed genes in
scrapie-infected brain tissue were enriched by the suppression
subtractive hybridization technique, molecularly cloned, and further
characterized. Northern blotting and nucleotide sequencing confirmed
the identities of 19 upregulated genes, 11 of which were unknown to be
affected by scrapie. A considerable number of these 19 genes, namely
those encoding interferon-inducible protein 10 (IP-10), 2',5'-oligo(A)
synthetase, Mx protein, IIGP protein, major histocompatibility complex
classes I and II, complement, and
2-microglobulin, were
inducible by interferons (IFNs), suggesting that an IFN response is a
possible mechanism of gene activation in scrapie. Among the newly found
genes, that coding for 2',5'-oligo(A) synthetase is of special interest
because it could contribute to the apoptotic loss of neuronal cells via
RNase L activation. In addition, upregulation of the chemokine IP-10
and B-lymphocyte chemoattractant mRNAs was seen at relatively early
stages of the disease and was sustained throughout disease development.
*
Corresponding author. Mailing address:
Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany. Phone:
49-30-45472230. Fax: 49-30-45472609. E-mail: baierm{at}rki.de.
Journal of Virology, November 2000, p. 10245-10248, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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