Summary of Study ST003335
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002074. The data can be accessed directly via it's Project DOI: 10.21228/M8HZ53 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003335 |
| Study Title | Biological stress metabolomics in Duchenne muscular dystrophy rodent model |
| Study Type | Biological Stress Discovery Targeted Metabolomics |
| Study Summary | Duchenne muscular dystrophy is a severe neuromuscular wasting disease that is caused by a primary defect in dystrophin protein and involves organism-wide comorbidities such as cardiomyopathy, metabolic and mitochondrial dysfunction, and non-progressive cognitive impairments. Physiological stress exposure in the mdx mouse model of Duchenne muscular dystrophy results in phenotypic abnormalities that include locomotor inactivity, hypotension, and increased morbidity. Severe and lethal stress susceptibility in mdx mice corresponds to metabolic dysfunction in several coordinated metabolic pathways within dystrophin-deficient skeletal muscle, as well as prolonged elevation in mdx plasma corticosterone levels that extends beyond the WT stress response. Here we performed a targeted mass spectrometry-based plasma metabolomics screen focused on biological stress pathways in healthy and dystrophin-deficient mdx mice exposed to mild scruff stress. One-third of the stress-relevant metabolites interrogated displayed significant elevation or depletion in mdx plasma after scruff stress and were restored to WT by skeletal muscle-specific dystrophin expression. The metabolic pathways of mdx mice altered by scruff stress are associated with regulation of the hypothalamic-pituitary-adrenal axis, locomotor tone, neurocognitive function, redox metabolism, cellular bioenergetics, and protein catabolism. Our data suggest that a mild stress triggers an exaggerated, multi-system metabolic response in mdx mice. |
| Institute | University of Minnesota |
| Department | Biochemistry, Molecular Biology, and Biophysics |
| Laboratory | James Ervasti |
| Last Name | Johnson |
| First Name | Erynn |
| Address | 420 Washington Ave SE |
| joh18358@umn.edu | |
| Phone | 4024054007 |
| Submit Date | 2024-07-19 |
| Num Groups | 6 |
| Total Subjects | 48 |
| Num Males | 48 |
| Analysis Type Detail | Other |
| Release Date | 2024-08-09 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002074 |
| Project DOI: | doi: 10.21228/M8HZ53 |
| Project Title: | Biological stress metabolomics in Duchenne muscular dystrophy rodent model |
| Project Type: | Biological Stress Discovery Targeted Metabolomics |
| Project Summary: | Our goal is to identify stress-relevant metabolomic alterations in dystrophin-deficient organisms following physiological stress exposure. Here we performed a targeted mass spectrometry-based plasma metabolomics screen through Metabolon that focused on biological stress pathways in healthy and dystrophin-deficient mdx mice exposed to mild scruff stress. One-third of the stress-relevant metabolites interrogated displayed significant elevation or depletion in mdx plasma after scruff stress and were restored to WT by skeletal muscle-specific dystrophin expression. The metabolic pathways of mdx mice altered by scruff stress are associated with regulation of the hypothalamic-pituitary-adrenal axis, locomotor tone, neurocognitive function, redox metabolism, cellular bioenergetics, and protein catabolism. Our data suggest that a mild stress triggers an exaggerated, multi-system metabolic response in mdx mice. |
| Institute: | University of Minnesota |
| Department: | Biochemistry, Molecular Biology, and Biophysics |
| Laboratory: | James Ervasti |
| Last Name: | Johnson |
| First Name: | Erynn |
| Address: | 420 Washington Ave SE |
| Email: | joh18358@umn.edu |
| Phone: | 4024054007 |
| Funding Source: | 5T32AR007612-21; 5T32AR007612-22; 5T32AG029796-13; 5T32AG029796-14; 5R01AR042423-27; 5R01AR049899-18 |
| Contributors: | Erynn E. Johnson; James M. Ervasti |
Subject:
| Subject ID: | SU003456 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | C57BL6/J; C57BL10/J; C57BL/10ScSn-Dmdmdx/J |
| Age Or Age Range: | 120-150 days |
| Weight Or Weight Range: | 25-35g |
| Height Or Height Range: | N/A |
| Gender: | Male |
| Animal Animal Supplier: | Jackson Laboratories |
| Animal Housing: | Research Animal Resources campus facilities |
| Animal Light Cycle: | 12h light/dark cycle |
| Animal Feed: | Standard chow |
| Animal Water: | Water bottle |
| Animal Inclusion Criteria: | Age; gender |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | GENOTYPE | TREATMENT | Sample source |
|---|---|---|---|---|
| SA362634 | UNMN-01559 | MDX | no stress | Blood plasma |
| SA362635 | UNMN-01582 | MDX | no stress | Blood plasma |
| SA362636 | UNMN-01581 | MDX | no stress | Blood plasma |
| SA362637 | UNMN-01580 | MDX | no stress | Blood plasma |
| SA362638 | UNMN-01583 | MDX | no stress | Blood plasma |
| SA362639 | UNMN-01558 | MDX | no stress | Blood plasma |
| SA362640 | UNMN-01556 | MDX | no stress | Blood plasma |
| SA362641 | UNMN-01557 | MDX | no stress | Blood plasma |
| SA362642 | UNMN-01595 | MDX | stress | Blood plasma |
| SA362643 | UNMN-01593 | MDX | stress | Blood plasma |
| SA362644 | UNMN-01572 | MDX | stress | Blood plasma |
| SA362645 | UNMN-01570 | MDX | stress | Blood plasma |
| SA362646 | UNMN-01569 | MDX | stress | Blood plasma |
| SA362647 | UNMN-01571 | MDX | stress | Blood plasma |
| SA362648 | UNMN-01596 | MDX | stress | Blood plasma |
| SA362649 | UNMN-01594 | MDX | stress | Blood plasma |
| SA362650 | UNMN-01564 | MTBD | no stress | Blood plasma |
| SA362651 | UNMN-01563 | MTBD | no stress | Blood plasma |
| SA362652 | UNMN-01562 | MTBD | no stress | Blood plasma |
| SA362653 | UNMN-01584 | MTBD | no stress | Blood plasma |
| SA362654 | UNMN-01561 | MTBD | no stress | Blood plasma |
| SA362655 | UNMN-01587 | MTBD | no stress | Blood plasma |
| SA362656 | UNMN-01586 | MTBD | no stress | Blood plasma |
| SA362657 | UNMN-01585 | MTBD | no stress | Blood plasma |
| SA362658 | UNMN-01560 | MTBD | no stress | Blood plasma |
| SA362659 | UNMN-01597 | MTBD | stress | Blood plasma |
| SA362660 | UNMN-01573 | MTBD | stress | Blood plasma |
| SA362661 | UNMN-01574 | MTBD | stress | Blood plasma |
| SA362662 | UNMN-01598 | MTBD | stress | Blood plasma |
| SA362663 | UNMN-01599 | MTBD | stress | Blood plasma |
| SA362664 | UNMN-01575 | MTBD | stress | Blood plasma |
| SA362665 | UNMN-01552 | WT | no stress | Blood plasma |
| SA362666 | UNMN-01579 | WT | no stress | Blood plasma |
| SA362667 | UNMN-01578 | WT | no stress | Blood plasma |
| SA362668 | UNMN-01577 | WT | no stress | Blood plasma |
| SA362669 | UNMN-01553 | WT | no stress | Blood plasma |
| SA362670 | UNMN-01555 | WT | no stress | Blood plasma |
| SA362671 | UNMN-01554 | WT | no stress | Blood plasma |
| SA362672 | UNMN-01576 | WT | no stress | Blood plasma |
| SA362673 | UNMN-01588 | WT | stress | Blood plasma |
| SA362674 | UNMN-01589 | WT | stress | Blood plasma |
| SA362675 | UNMN-01590 | WT | stress | Blood plasma |
| SA362676 | UNMN-01591 | WT | stress | Blood plasma |
| SA362677 | UNMN-01592 | WT | stress | Blood plasma |
| SA362678 | UNMN-01568 | WT | stress | Blood plasma |
| SA362679 | UNMN-01567 | WT | stress | Blood plasma |
| SA362680 | UNMN-01566 | WT | stress | Blood plasma |
| SA362681 | UNMN-01565 | WT | stress | Blood plasma |
| Showing results 1 to 48 of 48 |
Collection:
| Collection ID: | CO003449 |
| Collection Summary: | Blood was collected after euthanasia via cardiac puncture and plasma was extracted and stored at -80 degrees Celsius until sample submission to Metabolon. |
| Sample Type: | Blood (plasma) |
| Collection Method: | Blood was collected after euthanasia via cardiac puncture and was rotated end-over-end in EDTA-coated tubes for 15 minutes at room temperature. Samples were centrifuged for 10 minutes at 2,000xg at 4 degrees Celsius, then plasma supernatant was collected and stored at -80 degrees Celsius until sample submission to Metabolon. |
| Collection Location: | -80 degree freezer |
| Collection Frequency: | Single collection |
| Collection Duration: | 30 minutes |
| Volumeoramount Collected: | 200 microliters |
| Storage Conditions: | -80℃ |
| Collection Vials: | EDTA-coated centrifuge tubes |
| Storage Vials: | Centrifuge tubes |
| Collection Tube Temp: | 20-25 degrees Celsius |
| Additives: | EDTA |
Treatment:
| Treatment ID: | TR003465 |
| Treatment Summary: | Mice in the "no stress" group were euthanized and blood samples were collected following euthanasia. Mice in the "stress" group were monitored in open-field activity cages to measure total locomotion distance for 30 minutes, then were briefly handled by a standard scruff method for 30 seconds, followed by an additional 30 minute activity cage monitoring session and euthanasia/sample collection. |
| Treatment: | Scruff handling stress |
| Treatment Compound: | N/A |
| Treatment Route: | N/A |
| Treatment Dose: | N/A |
| Treatment Dosevolume: | N/A |
| Treatment Doseduration: | N/A |
| Treatment Vehicle: | N/A |
| Animal Vet Treatments: | N/A |
| Animal Anesthesia: | N/A |
| Animal Acclimation Duration: | N/A |
| Animal Fasting: | N/A |
| Animal Endp Euthanasia: | Tribromoethanol (Avertin) |
| Animal Endp Tissue Coll List: | Blood |
| Animal Endp Clinical Signs: | N/A |
Sample Preparation:
| Sampleprep ID: | SP003463 |
| Sampleprep Summary: | Plasma samples were pipetted in 200 microliter quantities into barcoded sample tubes and submitted to Metabolon for additional sample preparation and analysis. Sample preparation details are proprietary information held by Metabolon. |
| Processing Method: | N/A |
| Processing Storage Conditions: | On ice |
| Extraction Method: | N/A |
| Extract Enrichment: | N/A |
| Extract Cleanup: | N/A |
| Sample Resuspension: | N/A |
| Sample Derivatization: | N/A |
| Sample Spiking: | N/A |
| Subcellular Location: | N/A |
Combined analysis:
| Analysis ID | AN005464 | AN005465 | AN005466 | AN005467 |
|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | Reversed phase | HILIC |
| Chromatography system | Waters Acquity | Waters Acquity | Waters Acquity | Waters Acquity |
| Column | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) |
| MS Type | ESI | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | POSITIVE | NEGATIVE | NEGATIVE |
| Units | Peak Area | Peak Area | Peak Area | Peak Area |
Chromatography:
| Chromatography ID: | CH004149 |
| Chromatography Summary: | Low pH polar (LC/MS Pos early) |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters Acquity BEH C18 (100 x 2mm, 1.7um) |
| Column Temperature: | 40-50 |
| Flow Gradient: | Linear gradient from 5% B to 80% B over 3.35 minutes |
| Flow Rate: | 0.35 mL/min |
| Solvent A: | 100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5 |
| Solvent B: | 100% methanol; 0.1% formic acid; 0.05% PFPA, pH ~2.5 |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004150 |
| Chromatography Summary: | Low pH Lipophilic (LC/MS Pos late) |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters Acquity BEH C18 (100 x 2mm, 1.7um) |
| Column Temperature: | 40-50 |
| Flow Gradient: | Linear gradient from 40% B to 99.5% B over 1.0 minute, hold 99.5% B for 2.4 minutes. |
| Flow Rate: | 0.60 mL/min |
| Solvent A: | 100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5 |
| Solvent B: | 50% methanol/50% acetonitrile; 0.1% formic acid; 0.05% PFPA, pH ~2.5 |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004151 |
| Chromatography Summary: | High pH (LC/MS Neg) |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters Acquity BEH C18 (100 x 2mm, 1.7um) |
| Column Temperature: | 40-50 |
| Flow Gradient: | Linear gradient from 0.5 to 70% B over 4.0 minutes, then rapid gradient to 99% B in 0.5 minutes. |
| Flow Rate: | 0.35 mL/min |
| Solvent A: | 100% water; 6.5 mM ammonium bicarbonate, pH 8 |
| Solvent B: | 95% methanol/5% water; 6.5 mM ammonium bicarbonate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004152 |
| Chromatography Summary: | HILIC (LC/MS Polar Neg) |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) |
| Column Temperature: | 40-50 |
| Flow Gradient: | Linear gradient from 5% B to 50% B in 3.5 minutes, then linear gradient from 50% B to 95% B in 2 minutes. |
| Flow Rate: | 0.50 mL/min |
| Solvent A: | 15% water/5% methanol/80% acetonitrile; 10 mM ammonium formate, (effective pH 10.16 with NH4OH) |
| Solvent B: | 50% water/50% acetonitrile; 10 mM ammonium formate, (effective pH 10.60 with NH4OH) |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS005190 |
| Analysis ID: | AN005464 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Metabolon (LC/MS Pos early) |
| Ion Mode: | POSITIVE |
| MS ID: | MS005191 |
| Analysis ID: | AN005465 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Metabolon (LC/MS Pos late) |
| Ion Mode: | POSITIVE |
| MS ID: | MS005192 |
| Analysis ID: | AN005466 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Metabolon (LC/MS Neg) |
| Ion Mode: | NEGATIVE |
| MS ID: | MS005193 |
| Analysis ID: | AN005467 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Metabolon (LC/MS Polar) |
| Ion Mode: | NEGATIVE |
