{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Okada K"],"funding":["Yoshio Koide","The Yukihiko Miyata Memorial Trust for ALS Research","Takeda Science Foundation","Japan Agency for Medical Research and Development","Keio Medical Association and Keio University Grant-in-Aid for Encouragement of Young Medical Scientists","Japan ALS Association","Daiichi Sankyo Foundation of Life Science","Japan Society for the Promotion of Science"],"pagination":["3933-3948"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11684083"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["147(11)"],"pubmed_abstract":["Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice. Fus WT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal "],"journal":["Brain : a journal of neurology"],"pubmed_title":["Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis."],"pmcid":["PMC11684083"],"funding_grant_id":["JP20ek0109395","JP22bm0804003","JP22K15736","JP21H05278","21H02812","JP23kk0305024","JP23bm1423002","JP23bm1123046","JP20H00485","JP21wm0425009","JP21ek0109492","21K07281","JP20ek0109329"],"pubmed_authors":["Aoki M","Kuramoto J","Kobayashi R","Morimoto S","Okano H","Okada K","Suzuki N","Nishimoto Y","Ito D","Shibata S","Takahashi S","Nakahara J","Oguma Y","Kato C","Shinozaki M","Ikawa M","Warita H"],"additional_accession":[]},"is_claimable":false,"name":"Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis.","description":"Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice. Fus WT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-01T03:17:23.109Z","creation":"2026-06-01T03:06:16.538Z"},"accession":"S-EPMC11684083","cross_references":{"pubmed":["39312484"],"doi":["10.1093/brain/awae224"]}}