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.

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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.

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Study IDST003335
Study TitleBiological stress metabolomics in Duchenne muscular dystrophy rodent model
Study TypeBiological Stress Discovery Targeted Metabolomics
Study SummaryDuchenne 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
DepartmentBiochemistry, Molecular Biology, and Biophysics
LaboratoryJames Ervasti
Last NameJohnson
First NameErynn
Address420 Washington Ave SE
Emailjoh18358@umn.edu
Phone4024054007
Submit Date2024-07-19
Num Groups6
Total Subjects48
Num Males48
Analysis Type DetailOther
Release Date2024-08-09
Release Version1
Erynn Johnson Erynn Johnson
https://dx.doi.org/10.21228/M8HZ53
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id GENOTYPE TREATMENT Sample source
SA362634UNMN-01559MDX no stress Blood plasma
SA362635UNMN-01582MDX no stress Blood plasma
SA362636UNMN-01581MDX no stress Blood plasma
SA362637UNMN-01580MDX no stress Blood plasma
SA362638UNMN-01583MDX no stress Blood plasma
SA362639UNMN-01558MDX no stress Blood plasma
SA362640UNMN-01556MDX no stress Blood plasma
SA362641UNMN-01557MDX no stress Blood plasma
SA362642UNMN-01595MDX stress Blood plasma
SA362643UNMN-01593MDX stress Blood plasma
SA362644UNMN-01572MDX stress Blood plasma
SA362645UNMN-01570MDX stress Blood plasma
SA362646UNMN-01569MDX stress Blood plasma
SA362647UNMN-01571MDX stress Blood plasma
SA362648UNMN-01596MDX stress Blood plasma
SA362649UNMN-01594MDX stress Blood plasma
SA362650UNMN-01564MTBD no stress Blood plasma
SA362651UNMN-01563MTBD no stress Blood plasma
SA362652UNMN-01562MTBD no stress Blood plasma
SA362653UNMN-01584MTBD no stress Blood plasma
SA362654UNMN-01561MTBD no stress Blood plasma
SA362655UNMN-01587MTBD no stress Blood plasma
SA362656UNMN-01586MTBD no stress Blood plasma
SA362657UNMN-01585MTBD no stress Blood plasma
SA362658UNMN-01560MTBD no stress Blood plasma
SA362659UNMN-01597MTBD stress Blood plasma
SA362660UNMN-01573MTBD stress Blood plasma
SA362661UNMN-01574MTBD stress Blood plasma
SA362662UNMN-01598MTBD stress Blood plasma
SA362663UNMN-01599MTBD stress Blood plasma
SA362664UNMN-01575MTBD stress Blood plasma
SA362665UNMN-01552WT no stress Blood plasma
SA362666UNMN-01579WT no stress Blood plasma
SA362667UNMN-01578WT no stress Blood plasma
SA362668UNMN-01577WT no stress Blood plasma
SA362669UNMN-01553WT no stress Blood plasma
SA362670UNMN-01555WT no stress Blood plasma
SA362671UNMN-01554WT no stress Blood plasma
SA362672UNMN-01576WT no stress Blood plasma
SA362673UNMN-01588WT stress Blood plasma
SA362674UNMN-01589WT stress Blood plasma
SA362675UNMN-01590WT stress Blood plasma
SA362676UNMN-01591WT stress Blood plasma
SA362677UNMN-01592WT stress Blood plasma
SA362678UNMN-01568WT stress Blood plasma
SA362679UNMN-01567WT stress Blood plasma
SA362680UNMN-01566WT stress Blood plasma
SA362681UNMN-01565WT 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
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