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Expression from the gene encoding the beta-subunit of the S100 protein during development of the rodent brain

Posted on:1993-03-01Degree:Ph.DType:Dissertation
University:University of Toronto (Canada)Candidate:Landry, Charles FrancisFull Text:PDF
GTID:1474390014496984Subject:Biology
Abstract/Summary:
The calcium-binding protein, S100, is enriched in nervous tissue and conserved among vertebrates. The {dollar}beta{dollar}-subunit of S100 ({dollar}beta{dollar}-S100), which is the predominant form of S100 in the rodent brain, is found primarily within astrocytes and has been implicated in neurite extension. To examine the expression of {dollar}beta{dollar}-S100 during development of the rodent brain, the cDNA to the {dollar}beta{dollar}-subunit of S100 was isolated by antibody screening of a lambda gt11 expression library. {dollar}beta{dollar}-S100 cDNA recognized a single 1.6 kilobase mRNA species that increased progressively during postnatal rat brain development. Using in situ hybridization, {dollar}beta{dollar}-S100 mRNA was first observed prenatally in the ventricular region of the myelencephalon. The accumulation of {dollar}beta{dollar}-S100 mRNA was generally found to parallel the maturation of astrocytes although {dollar}beta{dollar}-S100 mRNA was also evident within astrocyte precursor cells and specific brain stem neurons. Further, {dollar}beta{dollar}-S100 mRNA was identified within craniofacial cartilage of the embryonic rat skull.; A comparison between the expression of {dollar}beta{dollar}-S100 mRNA and mRNA for the astrocyte protein, glial fibrillary acidic protein (GFAP) revealed that both mRNA species accumulated in parallel with the pattern of caudal-rostral brain maturation. Analysis at the cellular level identified differences in the pattern of expression of the two astrocyte mRNA species. While GFAP mRNA was abundant in astrocytes within white matter and the glial limitans during development, {dollar}beta{dollar}-S100 mRNA appeared to increase more gradually in astrocytes during brain maturation. The different patterns of expression of {dollar}beta{dollar}-S100 and GFAP mRNA highlight the independent regulation of the two astrocyte proteins and may reflect the differentiation of subpopulations of astrocytes.; To examine the influence of elevated levels of {dollar}beta{dollar}-S100 on mammalian development, mice transgenic for the human {dollar}beta{dollar}-S100 gene were generated. The pattern of expression of human {dollar}beta{dollar}-S100 mRNA in the brains of transgenic mice was similar to the endogenous pattern of {dollar}beta{dollar}-S100 expression. Both transgene and endogenous {dollar}beta{dollar}-S100 mRNA were localized to Bergmann glia of the cerebellum and to neurons within specific brain stem nuclei. Although elevated levels of human {dollar}beta{dollar}-S100 were evident within appropriate cell-types in the brain, neither histological nor physiological abnormalities were apparent in transgenic mice.
Keywords/Search Tags:S100, {dollar}beta{dollar}-s100, Brain, Protein, Expression, Development, Rodent
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