| First Author | Brettle M | Year | 2019 |
| Journal | Front Mol Neurosci | Volume | 12 |
| Pages | 231 | PubMed ID | 31611772 |
| Mgi Jnum | J:282177 | Mgi Id | MGI:6369887 |
| Doi | 10.3389/fnmol.2019.00231 | Citation | Brettle M, et al. (2019) Developmental Expression of Mutant PFN1 in Motor Neurons Impacts Neuronal Growth and Motor Performance of Young and Adult Mice. Front Mol Neurosci 12:231 |
| abstractText | 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 alpha-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. |
