Summary of Study ST002872

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 PR001794. The data can be accessed directly via it's Project DOI: 10.21228/M8TD9W 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 IDST002872
Study TitleComparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency
Study SummaryCardiomyopathy is often fatal in Friedreich Ataxia (FA). However, the FA heart maintains adequate function until disease end stage, suggesting that it can initially adapt to the loss of frataxin (FXN). Conditional knockout mouse models with no Fxn expression show transcriptional and metabolic profiles of cardiomyopathy and mitochondrial integrated stress response (ISRmt). However, ISRmt has not been investigated in models with disease-relevant, partial decrease of FXN. We characterized the heart transcriptomes and metabolomes of three mouse models of partial FXN loss, YG8-800, KIKO-700, and FxnG127V. Few metabolites were significantly changed in YG8-800 mice and did not provide a signature of cardiomyopathy or ISRmt. Instead, several metabolites were altered in FxnG127V and KIKO-700 hearts. Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FxnG127V hearts. However, these changes were surprisingly mild even at an advanced age (18-months), despite a severe decrease in FXN levels to 1% of WT. These findings indicate that the mouse heart has extremely low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.
Institute
Weill Cornell Medicine
Last NameSayles
First NameNicole
Address407 East 61st St, 5th Floor, New York, NY 10065
Emailnms2009@med.cornell.edu
Phone6469628172
Submit Date2023-02-01
Num Groups5
Total Subjects20
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2023-09-28
Release Version1
Nicole Sayles Nicole Sayles
https://dx.doi.org/10.21228/M8TD9W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001794
Project DOI:doi: 10.21228/M8TD9W
Project Title:Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency
Project Summary:Cardiomyopathy is often fatal in Friedreich Ataxia (FA). However, the FA heart maintains adequate function until disease end stage, suggesting that it can initially adapt to the loss of frataxin (FXN). Conditional knockout mouse models with no Fxn expression show transcriptional and metabolic profiles of cardiomyopathy and mitochondrial integrated stress response (ISRmt). However, ISRmt has not been investigated in models with disease-relevant, partial decrease of FXN. We characterized the heart transcriptomes and metabolomes of three mouse models of partial FXN loss, YG8-800, KIKO-700, and FxnG127V. Few metabolites were significantly changed in YG8-800 mice and did not provide a signature of cardiomyopathy or ISRmt. Instead, several metabolites were altered in FxnG127V and KIKO-700 hearts. Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FxnG127V hearts. However, these changes were surprisingly mild even at an advanced age (18-months), despite a severe decrease in FXN levels to 1% of WT. These findings indicate that the mouse heart has extremely low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.
Institute:Weill Cornell Medicine
Last Name:Nicole
First Name:Sayles
Address:407 East 61st St, 5th Floor, New York, NY 10065
Email:nms2009@med.cornell.edu
Phone:5167435432
Publications:https://journals.biologists.com/dmm/article/doi/10.1242/dmm.050114/328282/Comparative-multi-omics-analyses-of-cardiac

Subject:

Subject ID:SU002985
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

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

mb_sample_id local_sample_id Genotype Treatment
SA313922KOFemale_1030KIKO KIKO_700 F
SA313923KOFemale_1059KIKO KIKO_700 F
SA313924KOFemale_1061KIKO KIKO_700 F
SA313925KOMale_1040KIKO KIKO_700 M
SA313926KOMale_1042KIKO KIKO_700 M
SA313927KOMale_1069KIKO KIKO_700 M
SA313928MUTFemale_390Mutant G127V F
SA313929MUTFemale_340Mutant G127V F
SA313930MUTFemale_358Mutant G127V F
SA313931MUTMale_226Mutant G127V M
SA313932MUTMale_356Mutant G127V M
SA313933MUTMale_433Mutant G127V M
SA313934HeartY8PTgE_94Mutant YG8-800
SA313935HeartY8PTgE_50Mutant YG8-800
SA313936HeartY8PTgE_99Mutant YG8-800
SA313937HeartY8PTgE_96Mutant YG8-800
SA313938HeartEX2wt_93Wild-type Control
SA313939HeartEX2wt_51Wild-type Control
SA313940HeartEX2wt_184Wild-type Control
SA313941HeartEX2wt_199Wild-type Control
SA313942WTFemale_200Wild-type Control F
SA313943WTFemale_220Wild-type Control F
SA313944WTFemale_221Wild-type Control F
SA313945WTMale_218Wild-type Control M
SA313946WTMale_204Wild-type Control M
SA313947WTMale_207Wild-type Control M
Showing results 1 to 26 of 26

Collection:

Collection ID:CO002978
Collection Summary:Mice were anesthetized with pentobarbital. Hearts were extracted, washed in PBS and snap frozen in liquid nitrogen.
Sample Type:Heart

Treatment:

Treatment ID:TR002994
Treatment Summary:N/A

Sample Preparation:

Sampleprep ID:SP002991
Sampleprep Summary:15 mg of cardiac tissue was homogenized in 80% methanol (Sigma) using Tissue Tearer (BioSpec) on dry ice. Samples were incubated at -80ºC for 4 hours. Homogenates were then centrifuged at 14,000 rfc for 20 min at 4ºC. The supernatant was extracted and stored at -80ºC for mass spectroscopy (Weill Cornell Medicine Meyer Cancer Center Proteomics & Metabolomics Core Facility). Peak intensities for metabolites were screened for missing values and analyzed by using MetaboAnalyst software (version 5.0).

Combined analysis:

Analysis ID AN004708
Analysis type MS
Chromatography type HILIC
Chromatography system Thermo Vanquish
Column SeQuant ZIC-pHILIC (150 x 2.1mm, 5um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units Peak intensity

Chromatography:

Chromatography ID:CH003545
Instrument Name:Thermo Vanquish
Column Name:SeQuant ZIC-pHILIC (150 x 2.1mm, 5um)
Column Temperature:30
Flow Gradient:85% to 30% acetonitrile (ACN)
Flow Rate:150 μL/min
Solvent A:0.1% NH4OH/20 mM CH3COONH4
Solvent B:100% acetonitrile
Chromatography Type:HILIC

MS:

MS ID:MS004454
Analysis ID:AN004708
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition Comments: The Q Exactive was operated in full scan, polarity-switching mode with the following parameters: the spray voltage 3.0 kV, the heated capillary temperature 300 °C, the HESI probe temperature 350 °C, the sheath gas flow 40 units, the auxiliary gas flow 15 units. MS data acquisition was performed in the m/z range of 70–1,000, with 70,000 resolution (at 200 m/z). Data processing Comments: The MS data was processed using XCalibur 4.1 (Thermo Scientific) to extract the metabolite signal intensity for relative quantitation. Metabolites were identified using an in-house library established using chemical standards. Identification required exact mass (within 5ppm) and standard retention times. Software/procedures used for feature assignments: The MS data was processed using XCalibur 4.1 (Thermo Scientific) to extract the metabolite signal intensity for relative quantitation. Metabolites were identified using an in-house library established using chemical standards. Identification required exact mass (within 5ppm) and standard retention times.
Ion Mode:POSITIVE
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