Loss of mouse Stmn2 function causes motor neuropathy.
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.
Pubmed ID: 35294901 RIS Download
Research resources used in this publication
- Image Studio Lite (RRID:SCR_013715) (software resource)
- Harvard Center for Biological Imaging Core Facility (RRID:SCR_018673) (service resource)
- Biorender (RRID:SCR_018361) (web application)
- Geneious (RRID:SCR_010519) (software resource)
- CellProfiler Image Analysis Software (RRID:SCR_007358) (data processing software)
- GraphPad Prism (RRID:SCR_002798) (software resource)
- Fiji (RRID:SCR_002285) (software resource)
- STMN2 antibody (RRID:AB_10900514) (antibody)
- Anti-SCG10 antibody [EPR15286-39] (RRID:AB_2773045) (antibody)
Additional research tools detected in this publication
Antibodies used in this publication
- STMN2 antibody (RRID:AB_10900514)
- Anti-SCG10 antibody [EPR15286-39] (RRID:AB_2773045)
- α-Bungarotoxin, Alexa Fluor 555 conjugate (RRID:AB_2617152)
- Mouse Osteopontin (OPN) Affinity Purified Polyclonal Ab (RRID:AB_2194992)
- Anti-tubulin polyAb pan specific (sheep) + control (RRID:AB_10708807)
- Mouse Anti-Beta-III Tubulin Monoclonal antibody, Biotin Conjugated, Clone tuj-1 (RRID:AB_356859)
- Anti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5 (RRID:AB_2107445)
- Rabbit Anti-TDP43 Polyclonal Antibody, Unconjugated (RRID:AB_2271509)
- Anti-IBA 1 (RRID:AB_2493179)
- Anti-Choline Acetyltransferase Antibody (RRID:AB_2079751)
- GFAP Monoclonal Antibody (2.2B10) (RRID:AB_2532994)
- STMN2 Antibody (RRID:AB_10011569)
- Synaptophysin (7H12) Mouse mAb (IF Formulated) #9020 (RRID:AB_2631095)
Associated grants
- Agency: NIA NIH HHS, United States
Id: K99 AG057808 - Agency: NINDS NIH HHS, United States
Id: R01 NS089742
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This is a list of tools and resources that we have found mentioned in this publication.
Novus Biologicals (tool)
RRID:SCR_004286
Commercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsCHOPCHOP (tool)
RRID:SCR_015723
Web application for designing gRNAs for CRISPR/Cas9 experiments. It selects target sites for CRISPR/Cas9, CRISPR/Cpf1 or TALEN-directed mutagenesis.
View all literature mentionsC57BL/6J (tool)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsSTMN2 antibody (antibody)
RRID:AB_10900514
This polyclonal targets STMN2 antibody
View all literature mentionsAnti-SCG10 antibody [EPR15286-39] (antibody)
RRID:AB_2773045
This monoclonal targets SCG10
View all literature mentionsα-Bungarotoxin, Alexa Fluor 555 conjugate (antibody)
RRID:AB_2617152
This unknown targets α-subunit of the nicotinic acetylcholine receptor (AChR) of neuromuscular junction
View all literature mentionsMouse Osteopontin (OPN) Affinity Purified Polyclonal Ab (antibody)
RRID:AB_2194992
This polyclonal targets Mouse Osteopontin (OPN) Affinity Purified Ab
View all literature mentionsAnti-tubulin polyAb pan specific (sheep) + control (antibody)
RRID:AB_10708807
This polyclonal targets tubulin
View all literature mentionsMouse Anti-Beta-III Tubulin Monoclonal antibody, Biotin Conjugated, Clone tuj-1 (antibody)
RRID:AB_356859
This monoclonal targets beta-III Tubulin
View all literature mentionsAnti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5 (antibody)
RRID:AB_2107445
This monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsRabbit Anti-TDP43 Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_2271509
This polyclonal targets Tardbp
View all literature mentionsAnti-Choline Acetyltransferase Antibody (antibody)
RRID:AB_2079751
This polyclonal targets Choline Acetyltransferase
View all literature mentionsGFAP Monoclonal Antibody (2.2B10) (antibody)
RRID:AB_2532994
This monoclonal targets GFAP
View all literature mentionsSynaptophysin (7H12) Mouse mAb (IF Formulated) #9020 (antibody)
RRID:AB_2631095
This monoclonal targets Synaptophysin
View all literature mentionsImage Studio Lite (software resource)
RRID:SCR_013715
THIS RESOURCE IS NO LONGER IN SERVICE. Documented on September 28,2023. Software application which can analyze basic Western blot data and export them for use in spreadsheet programs. Users can create standardized or custom lab reports and can share them with colleagues. Image Studio Lite has been discontinued and replaced with Empiria Studio Software.
View all literature mentionsHarvard Center for Biological Imaging Core Facility (service resource)
RRID:SCR_018673
Microscopy facility. Contains microscopes including confocal, super-resolution, multi-photon, light sheet, live cell imaging, high-content screening, slide scanning, laser dissection and macroscopy stations. Features wet lab space, eukaryotic and prokaryotic incubation, and access to nearby animal care facilities for wide range of species.Services include Cell Imaging,Confocal Microscopy,Consultations,Data Analysis,Data Processing And Interpretation,High Content Screening,Laser Capture Microdissection,Microscopy,Multiphoton Microscopy,Optical Imaging,Slide Scanning,Whole Slide Imaging.
View all literature mentionsBiorender (web application)
RRID:SCR_018361
Web tool for graphical illustrations for biological systems by BioRender. Used for articles and presentations. Collection of pre made icons and templates from life science fields for scientific illustrations. Customized icons possible on request.
View all literature mentionsGeneious (software resource)
RRID:SCR_010519
Software package for sequence alignment, assembly and analysis. Integrated and extendable desktop software platform for organization and analysis of sequence data. Bioinformatics software platform packed with molecular biology and sequence analysis tools.
View all literature mentionsCellProfiler Image Analysis Software (data processing software)
RRID:SCR_007358
Software tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsFiji (software resource)
RRID:SCR_002285
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsSTMN2 antibody (antibody)
RRID:AB_10900514
This polyclonal targets STMN2 antibody
View all literature mentionsAnti-SCG10 antibody [EPR15286-39] (antibody)
RRID:AB_2773045
This monoclonal targets SCG10
View all literature mentions
