| Autor: |
Brettle, Merryn, Stefen, Holly, Djordjevic, Aleksandra, Fok, Sandra Y. Y., Chan, Josephine W., van Hummel, Annika, van der Hoven, Julia, Przybyla, Magdalena, Volkerling, Alexander, Ke, Yazi D., Delerue, Fabien, Ittner, Lars M., Fath, Thomas |
| Předmět: |
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| Zdroj: |
Frontiers in Molecular Neuroscience; 9/27/2019, p1-12, 12p |
| Abstrakt: |
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment and no cure. Mutations in profilin 1 were identified as a cause of familial ALS (fALS) in 2012. We investigated the functional impact of mutant profilin 1 expression in spinal cords during mouse development. We developed a novel mouse model with the expression of profilin 1 C71G under the control of the Hb9 promoter, targeting expression to α-motor neurons in the spinal cord during development. Embryos of transgenic mice showed evidence of a significant reduction of brachial nerve diameter and a loss of Mendelian inheritance. Despite the lack of transgene expression, adult mice presented with significant motor deficits. Transgenic mice had a significant reduction in the number of motor neurons in the spinal cord. Further analysis of these motor neurons in aged transgenic mice revealed reduced levels of TDP-43 and ChAT expression. Although profilin 1 C71G was only expressed during development, adult mice presented with some ALS-associated pathology and motor symptoms. This study highlights the effect of profilin 1 during neurodevelopment and the impact that this may have in later ALS. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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