Loss of mouse Stmn2 function causes motor neuropathy

Autor:	Irune Guerra San Juan, Leslie A. Nash, Kevin S. Smith, Marcel F. Leyton-Jaimes, Menglu Qian, Joseph R. Klim, Francesco Limone, Alexander B. Dorr, Alexander Couto, Greta Pintacuda, Brian J. Joseph, D. Eric Whisenant, Caroline Noble, Veronika Melnik, Deirdre Potter, Amie Holmes, Aaron Burberry, Matthijs Verhage, Kevin Eggan
Přispěvatelé:	Functional Genomics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Rok vydání:	2022
Předmět:	Motor Neurons neuromuscular junction General Neuroscience Amyotrophic Lateral Sclerosis Homozygote Mice Transgenic Article microtubules stathmin 2 Disease Models Animal Mice SCG10 CRISPR Animals Stathmin ALS motor neuropathy TDP43 motor neuron TARDBP
Zdroj:	Neuron Neuron, 110(10), 1671-1688.e6. Cell Press Guerra San Juan, I, Nash, L A, Smith, K S, Leyton-Jaimes, M F, Qian, M, Klim, J R, Limone, F, Dorr, A B, Couto, A, Pintacuda, G, Joseph, B J, Whisenant, D E, Noble, C, Melnik, V, Potter, D, Holmes, A, Burberry, A, Verhage, M & Eggan, K 2022, ' Loss of mouse Stmn2 function causes motor neuropathy ', Neuron, vol. 110, no. 10, pp. 1671-1688.e6 . https://doi.org/10.1016/j.neuron.2022.02.011
ISSN:	0896-6273
Popis:	Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration accompanied by aberrant accumulation and loss of function of the RNA-binding protein TDP43. Thus far, it remains unresolved to what extent TDP43 loss of function directly contributes to motor system dysfunction. Here, we employed gene editing to find whether the mouse ortholog of the TDP43-regulated gene STMN2 has an important function in maintaining the motor system. Both mosaic founders and homozygous loss-of-function Stmn2 mice exhibited neuromuscular junction denervation and fragmentation, resulting in muscle atrophy and impaired motor behavior, accompanied by an imbalance in neuronal microtubule dynamics in the spinal cord. The introduction of human STMN2 through BAC transgenesis was sufficient to rescue the motor phenotypes observed in Stmn2 mutant mice. Collectively, our results demonstrate that disrupting the ortholog of a single TDP43-regulated RNA is sufficient to cause substantial motor dysfunction, indicating that disruption of TDP43 function is likely a contributor to ALS.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74f8b793528a00714433808ce22c13f6 https://doi.org/10.1016/j.neuron.2022.02.011 Zobrazit plný text záznamu