Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model
Date of Original Version
Biomedical and Pharmaceutical Sciences
Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of the tau protein in the human brain. The best known of these illnesses is Alzheimer’s disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse model was tested for the transgene’s ability to respond to an environmental toxicant. Pups were developmentally exposed to lead (Pb) from postnatal day (PND) 1-20 with 0.2% Pb acetate. Mice were then sacrificed at PND 20, 30, 40 and 60. Protein and mRNA levels for tau and CDK5 as well as tau phosphorylation at Ser396 were determined. In addition, the potential role of miRNA in tau expression was investigated by measuring levels of miR-34c, a miRNA that targets the mRNA for human tau, at PND20 and 50. The expression of the human tau transgene was altered by developmental exposure to Pb. This exposure also altered the expression of miR-34c. Our findings are the first of their kind to test the responsiveness of the human tau gene to an environmental toxicant and to examine an epigenetic mechanism that may be involved in the regulation of this gene’s expression.
Dash, M., Eid, A., Subaiea, G., Chang, J., Deeb, R., Masoud, A., Renehan, W. E.,...Zawia, N. H. (2012). Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model. NeuroToxicology, 55, 154-159. doi: 10.1016/j.neuro.2016.06.001
Available at: https://doi.org/10.1016/j.neuro.2016.06.001
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M. Dash, A. Eid, R. Deeb, William E. Renehan and Nasser H. Zawia are in the Interdisciplinary Neurosciences.
J. Chang, A. Masoud, William E. Renehan and Nasser H. Zawia are in the Department of Biomedical and Pharmaceutical Sciences.
This is a pre-publication author manuscript of the final, published article.