An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus
Abstract Dysfunction of Elongator is associated with amyotrophic lateral sclerosis (ALS). Here, we describe mouse models in which either Elongator subunit 1(Elp1) or subunit 3 (Elp3) is selectively ablated in alpha motor neurons of the spinal cord. These mice exhibit a progressive loss of motor stre...
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08701-9 |
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| author | Magge Snow BreAnna Cameron Renzie Pond Rachel Trudell Sara Snyder Lauryn Torres-Hernandez Devyn Deschamps Danara Tulimaiau Kiana Hawkinson Morgan Russell Danielle Horan Joseph Walters James H. Fox Britni Arlian Alain Chariot Laurent Nguyen Lynn George |
| author_facet | Magge Snow BreAnna Cameron Renzie Pond Rachel Trudell Sara Snyder Lauryn Torres-Hernandez Devyn Deschamps Danara Tulimaiau Kiana Hawkinson Morgan Russell Danielle Horan Joseph Walters James H. Fox Britni Arlian Alain Chariot Laurent Nguyen Lynn George |
| author_sort | Magge Snow |
| collection | DOAJ |
| description | Abstract Dysfunction of Elongator is associated with amyotrophic lateral sclerosis (ALS). Here, we describe mouse models in which either Elongator subunit 1(Elp1) or subunit 3 (Elp3) is selectively ablated in alpha motor neurons of the spinal cord. These mice exhibit a progressive loss of motor strength and motor neuron degeneration. To interrogate the molecular mechanisms that contribute to motor neuron cell death in these mice, we examine multiple disease pathways, including the expression of TDP-43 whose cytoplasmic aggregation is associated with the human disease. Although TDP-43 is a well-characterized nuclear protein functioning in RNA metabolism and gene transcription, here we document TDP-43’s robust presence in the nucleolus of wild-type motor neurons and its clearance from both the nucleus and the nucleolus of motor neurons in Elp conditional knockout mice. Thus, this study directly links dysfunction of Elongator with nucleolar disruption and TDP-43 clearing, two hallmark cellular pathologies of ALS. |
| format | Article |
| id | doaj-art-b4c526951a3d4b79a556eafefa269299 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-b4c526951a3d4b79a556eafefa2692992025-08-24T11:46:07ZengNature PortfolioCommunications Biology2399-36422025-08-018111110.1038/s42003-025-08701-9An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolusMagge Snow0BreAnna Cameron1Renzie Pond2Rachel Trudell3Sara Snyder4Lauryn Torres-Hernandez5Devyn Deschamps6Danara Tulimaiau7Kiana Hawkinson8Morgan Russell9Danielle Horan10Joseph Walters11James H. Fox12Britni Arlian13Alain Chariot14Laurent Nguyen15Lynn George16Department of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Biological and Physical Sciences, Montana State University BillingsDepartment of Chemistry and Biochemistry, Montana State UniversityDepartment of Biological and Physical Sciences, Montana State University BillingsAnimal Resources Center, Montana State UniversityDepartment of Biological and Physical Sciences, Montana State University BillingsLaboratory of Cancer Biology, Interdisciplinary GIGA Institute, University of LiègeWELBIO Department, WEL Research InstituteDepartment of Biological and Physical Sciences, Montana State University BillingsAbstract Dysfunction of Elongator is associated with amyotrophic lateral sclerosis (ALS). Here, we describe mouse models in which either Elongator subunit 1(Elp1) or subunit 3 (Elp3) is selectively ablated in alpha motor neurons of the spinal cord. These mice exhibit a progressive loss of motor strength and motor neuron degeneration. To interrogate the molecular mechanisms that contribute to motor neuron cell death in these mice, we examine multiple disease pathways, including the expression of TDP-43 whose cytoplasmic aggregation is associated with the human disease. Although TDP-43 is a well-characterized nuclear protein functioning in RNA metabolism and gene transcription, here we document TDP-43’s robust presence in the nucleolus of wild-type motor neurons and its clearance from both the nucleus and the nucleolus of motor neurons in Elp conditional knockout mice. Thus, this study directly links dysfunction of Elongator with nucleolar disruption and TDP-43 clearing, two hallmark cellular pathologies of ALS.https://doi.org/10.1038/s42003-025-08701-9 |
| spellingShingle | Magge Snow BreAnna Cameron Renzie Pond Rachel Trudell Sara Snyder Lauryn Torres-Hernandez Devyn Deschamps Danara Tulimaiau Kiana Hawkinson Morgan Russell Danielle Horan Joseph Walters James H. Fox Britni Arlian Alain Chariot Laurent Nguyen Lynn George An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus Communications Biology |
| title | An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus |
| title_full | An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus |
| title_fullStr | An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus |
| title_full_unstemmed | An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus |
| title_short | An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus |
| title_sort | elongator mouse model of als spotlights tdp 43 in the motor neuron nucleolus |
| url | https://doi.org/10.1038/s42003-025-08701-9 |
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