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Journal of Neuroscience, Vol 12, 4337-4346, Copyright © 1992 by Society for Neuroscience
Cell-specific expression of high levels of human S100 beta in transgenic mouse brain is dependent on gene dosage
WC Friend, S Clapoff, C Landry, LE Becker, D O'Hanlon, RJ Allore, IR Brown, A Marks, J Roder and RJ Dunn
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
The beta-subunit of S100 protein (S100 beta) is highly conserved in the
mammalian brain. The gene coding for human S100 beta has been mapped to
chromosome 21. In order to study the consequences of overexpression of the
S100 beta gene, transgenic mice were generated by microinjection of a 17.3
kilobase human genomic fragment containing the three exons and the
transcription control elements of the human S100 beta gene. Mice from four
transgenic lines carried approximately 10-100 transgene copies. Northern
blotting demonstrated a tissue-specific and gene dose- dependent expression
of human S100 beta mRNA in mouse brain. Increased expression of S100 beta
mRNA was correlated with an increased production of S100 beta protein.
Examination of brain sections by in situ hybridization and
immunocytochemistry indicated that S100 beta was localized globally to
astrocytes, as well as to discrete neurons in the mesencephalic and motor
trigeminal, facial, and lemniscus nuclei in both normal and transgenic
mice. In peripheral tissues, human S100 beta was expressed at 10-50-fold
lower levels than in brain. The strict gene dosage dependence and cell
specificity of transgene expression suggest the presence of a locus control
region (LCR) in the human S100 beta gene. The mice tolerated 10-100-fold
higher than normal levels of S100 beta gene expression in brain without any
gross physical or behavioral abnormalities. The high-level expression and
cell specificity of the S100 beta promoter/LCR suggest that it may provide
a valuable tool to direct the expression of other transgenic products to
specific cell types in the CNS.
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