Developmental Expression of Mutant PFN1 in Motor Neurons Impacts Neuronal Growth and Motor Performance of Young and Adult Mice
Autor: | Merryn Brettle, Holly Stefen, Aleksandra Djordjevic, Sandra Y. Y. Fok, Josephine W. Chan, Annika van Hummel, Julia van der Hoven, Magdalena Przybyla, Alexander Volkerling, Yazi D. Ke, Fabien Delerue, Lars M. Ittner, Thomas Fath |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Genetically modified mouse medicine.medical_specialty amyotrophic lateral sclerosis Transgene Mutant macromolecular substances Biology lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine medicine motor neurons Amyotrophic lateral sclerosis lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Molecular Biology Actin Original Research Neurodegeneration neurodegeneration Embryo medicine.disease Spinal cord 030104 developmental biology Endocrinology medicine.anatomical_structure actin 030217 neurology & neurosurgery Neuroscience profilin 1 |
Zdroj: | Frontiers in Molecular Neuroscience Frontiers in Molecular Neuroscience, Vol 12 (2019) |
ISSN: | 1662-5099 |
Popis: | 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. |
Databáze: | OpenAIRE |
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