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Part 1: Document Description
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Citation |
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Title: |
Expression of a protein disulfide isomerase A3 variant associated to amyotrophic lateral sclerosis triggers disease features in mice |
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Identification Number: |
doi:10.34691/UCHILE/Z9SEHC |
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Distributor: |
Repositorio de datos de investigación de la Universidad de Chile |
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Date of Distribution: |
2024-07-09 |
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Version: |
2 |
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Bibliographic Citation: |
Hetz, Claudio; Danilo B. Medinas; Juan Pablo Henriquez; Ute Woehlbier; Bredford Kerr; Guillermo Diaz; Amparo Zuleta; Matías Mansilla-Jaramillo; Pablo Rozas; Jessica Mella; Jorge Ojeda; Viviana Perez; Patricia Ojeda; Francisca Martinez-Traub1; Martin Sepulveda, 2024, "Expression of a protein disulfide isomerase A3 variant associated to amyotrophic lateral sclerosis triggers disease features in mice", https://doi.org/10.34691/UCHILE/Z9SEHC, Repositorio de datos de investigación de la Universidad de Chile, V2 |
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Citation |
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Title: |
Expression of a protein disulfide isomerase A3 variant associated to amyotrophic lateral sclerosis triggers disease features in mice |
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Identification Number: |
doi:10.34691/UCHILE/Z9SEHC |
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Authoring Entity: |
Hetz, Claudio (Universidad de Chile - Facultad de Medicina) |
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Danilo B. Medinas (Universidad de Chile - Facultad de Medicina) |
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Juan Pablo Henriquez (Universidad de Chile - Facultad de Medicina) |
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Ute Woehlbier (Universidad de Chile - Facultad de Medicina) |
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Bredford Kerr (Universidad de Chile - Facultad de Medicina) |
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Guillermo Diaz (Universidad de Chile - Facultad de Medicina) |
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Amparo Zuleta (Universidad de Chile - Facultad de Medicina) |
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Matías Mansilla-Jaramillo (Universidad de Chile - Facultad de Medicina) |
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Pablo Rozas (Universidad de Chile - Facultad de Medicina) |
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Jessica Mella (Universidad de Chile - Facultad de Medicina) |
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Jorge Ojeda (Universidad de Chile - Facultad de Medicina) |
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Viviana Perez (Universidad de Chile - Facultad de Medicina) |
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Patricia Ojeda (Universidad de Chile - Facultad de Medicina) |
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Francisca Martinez-Traub1 (Universidad de Chile - Facultad de Medicina) |
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Martin Sepulveda (Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chil) |
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Distributor: |
Repositorio de datos de investigación de la Universidad de Chile |
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Access Authority: |
Hetz, Claudio |
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Depositor: |
Hetz, Claudio |
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Date of Deposit: |
2024-07-09 |
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Holdings Information: |
https://doi.org/10.34691/UCHILE/Z9SEHC |
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Study Scope |
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Keywords: |
Medicine, Health and Life Sciences |
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Abstract: |
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motoneurons and compromised proteostasis. Dysfunction of the endoplasmic reticulum (ER) has been identified as a transversal pathogenic mechanism associated to motoneurons vulnerability in ALS. Protein disulfide isomerases (PDIs) are key enzymes catalyzing protein folding at the ER that are altered in the disease, involving both biochemical and genetic perturbations. We previously identified mutations in the gene encoding PDIA3 (also known as Grp58 or ERp57) in ALS cases, which were associated with altered neurite outgrowth in cell culture and abnormal motoneuron connectivity in zebrafish. Here we report the generation of transgenic mice expressing the ALS-associated PDIA3Q481K variant. Moderate PDIA3Q481K overexpression resulted in altered motor capacity accompanied by decreased motoneurons number and induction of ER stress in the spinal cord. The adverse effects of PDIA3Q481K were associated with altered electromyogram without evident morphological changes in neuromuscular junctions. Our results suggest that the PDIA3Q481K variant is pathogenic and its overexpression in mice recapitulate some ALS features, further supporting the concept that altered proteostasis due to PDI dysfunction constitute a risk factor to develop the disease. |
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Methodology and Processing |
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Sources Statement |
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Data Access |
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Other Study Description Materials |
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Fig 2 A-E.pzfx |
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Fig 3 A-E, Fig S1 and Fig S2.pzfx |
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Sepulveda et al HMG 20240708.docx |
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Sepulveda et al 2024 Figures corrected.pptx |
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Sepulveda et al 2024 raw datasets.xlsx |
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Sepulveda et al 2024 raw images.pptx |
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