Summary of study ST000352

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 PR000281. The data can be accessed directly via it's Project DOI: 10.21228/M8KW38 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST000352
Study TitleMetabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease
Study TypeAnimal hindbrain comparison
Study SummaryP15 wildtype mouse hindbrains, P15 twitcher mouse hindbrains, P22 wildtype mouse hindbrains, P22 twitcher mouse hindbrains
Institute
University at Buffalo
DepartmentHunter James Kelly Research Institute
LaboratoryShin Laboratory
Last NameShin
First NameDaesung
AddressNYS Center of Excellence in Bioinformatics & Life Sciences, 701 Ellicott Street, Buffalo, NY 14203
Emaildaesungs@buffalo.edu
Phone716-881-8980
Submit Date2016-02-02
Num Groups4
Total Subjects32
Raw Data AvailableYes
Analysis Type DetailGC/LC-MS
Release Date2016-03-03
Release Version1
Daesung Shin Daesung Shin
https://dx.doi.org/10.21228/M8KW38
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000281
Project DOI:doi: 10.21228/M8KW38
Project Title:Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease
Project Type:Disease Profiling
Project Summary:Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression if performed presymptomatically, but carries a significant risk of morbidity and mortality. Accurate presymptomatic diagnosis is therefore critical to facilitate the efficacy of existing transplant approaches and avoid unnecessary treatment of children who will not develop KD. Unfortunately current diagnostic criteria, including GALC activity, genetic analysis, and psychosine measurement, are insufficient for secure presymptomatic diagnosis. Herein, we performed a global metabolomic analysis to identify pathogenetic metabolic pathways and novel biomarkers implicated in the authentic mouse model of KD, twitcher. At a time point before onset of signs of disease, twitcher hindbrains had metabolic profiles similar to wild type, with the exception of a decrease in metabolites related to glucose energy metabolism. Instead, many metabolic pathways were altered after early signs of disease in the twitcher, including decreased phospholipid turnover, restricted mitochondrial metabolism of branched-chain amino acids, increased inflammation, neurotransmitter metabolism and osmolytes. Hypoxanthine, a purine derivative, is increased before signs of disease appear, suggesting its potential as a biomarker for early diagnosis of KD. Additionally, given the early changes in glucose metabolism in the pathogenesis of KD, diagnostic modalities that report metabolic function, such as positron emission tomography, may be useful in KD.
Institute:University at Buffalo
Department:Hunter James Kelly Research Institute
Laboratory:Shin Laboratory
Last Name:Shin
First Name:Daesung
Address:NYS Center of Excellence in Bioinformatics & Life Sciences, 701 Ellicott Street, Buffalo, NY 14203
Email:daesungs@buffalo.edu
Phone:716-881-8980

Subject:

Subject ID:SU000372
Subject Type:Animal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6N|C57BL/6N Twitcher
Age Or Age Range:P15-P22 days
Species Group:Mammal

Factors:

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

mb_sample_id local_sample_id age genotype
SA015419UBUF-00099P15 Twitcher
SA015420UBUF-00100P15 Twitcher
SA015421UBUF-00101P15 Twitcher
SA015422UBUF-00102P15 Twitcher
SA015423UBUF-00103P15 Twitcher
SA015424UBUF-00104P15 Twitcher
SA015425UBUF-00105P15 Twitcher
SA015426UBUF-00106P15 Twitcher
SA015427UBUF-00091P15 Wild Type
SA015428UBUF-00092P15 Wild Type
SA015429UBUF-00093P15 Wild Type
SA015430UBUF-00094P15 Wild Type
SA015431UBUF-00095P15 Wild Type
SA015432UBUF-00096P15 Wild Type
SA015433UBUF-00097P15 Wild Type
SA015434UBUF-00098P15 Wild Type
SA015435UBUF-00115P22 Twitcher
SA015436UBUF-00116P22 Twitcher
SA015437UBUF-00117P22 Twitcher
SA015438UBUF-00118P22 Twitcher
SA015439UBUF-00119P22 Twitcher
SA015440UBUF-00120P22 Twitcher
SA015441UBUF-00121P22 Twitcher
SA015442UBUF-00122P22 Twitcher
SA015443UBUF-00107P22 Wild Type
SA015444UBUF-00108P22 Wild Type
SA015445UBUF-00109P22 Wild Type
SA015446UBUF-00110P22 Wild Type
SA015447UBUF-00111P22 Wild Type
SA015448UBUF-00112P22 Wild Type
SA015449UBUF-00113P22 Wild Type
SA015450UBUF-00114P22 Wild Type
Showing results 1 to 32 of 32

Collection:

Collection ID:CO000366
Collection Summary:None
Collection Protocol ID:COL_PROT
Collection Protocol Filename:pathogenesis_Krabbe_collection_protocol.pdf
Sample Type:Hindbrain (pons, medulla, brainstem, cerebellum)
Volumeoramount Collected:entire hindbrain

Treatment:

Treatment ID:TR000386
Treatment Summary:none

Sample Preparation:

Sampleprep ID:SP000379
Sampleprep Summary:None
Processing Method:Homogenization
Processing Storage Conditions:On Ice
Organ:Brain
Organ Specification:Hindbrain

Combined analysis:

Analysis ID AN000572 AN000573 AN000574
Analysis type MS MS MS
Chromatography type UPLC UPLC GC
Chromatography system Waters ACQUITY UPLC Waters ACQUITY UPLC See document
Column See doc See doc See document
MS Type ESI ESI EI
MS instrument type Single quadrupole Single quadrupole Single quadrupole
MS instrument name Thermo LTQ Thermo LTQ Thermo Trace DSQ
Ion Mode POSITIVE NEGATIVE POSITIVE
Units Peak height Peak height Peak height

Chromatography:

Chromatography ID:CH000409
Chromatography Summary:Experiments were conducted according to the protocols approved by the Institutional Animal Care and Use Committee of University at Buffalo and Roswell Park Cancer Institute. Twitcher mice were maintained on the background of C57BL/6N. Breeder C57BL/6N mice were purchased from Charles River. Freshly collected hindbrain regions from twitcher and WT littermate mice at P8, P15, P22, and P34 days were transferred into polypropylene cryovials, and then frozen in liquid nitrogen and stored at - 80°C until the analysis.
Methods Filename:pathogenesis_Krabbe_protocol.pdf
Instrument Name:Waters ACQUITY UPLC
Column Name:See doc
Chromatography Type:UPLC
  
Chromatography ID:CH000410
Chromatography Summary:Experiments were conducted according to the protocols approved by the Institutional Animal Care and Use Committee of University at Buffalo and Roswell Park Cancer Institute. Twitcher mice were maintained on the background of C57BL/6N. Breeder C57BL/6N mice were purchased from Charles River. Freshly collected hindbrain regions from twitcher and WT littermate mice at P8, P15, P22, and P34 days were transferred into polypropylene cryovials, and then frozen in liquid nitrogen and stored at - 80°C until the analysis.
Methods Filename:pathogenesis_Krabbe_protocol.pdf
Instrument Name:See document
Column Name:See document
Solvent A:5% phenyl
Chromatography Type:GC

MS:

MS ID:MS000508
Analysis ID:AN000572
Instrument Name:Thermo LTQ
Instrument Type:Single quadrupole
MS Type:ESI
Ion Mode:POSITIVE
  
MS ID:MS000509
Analysis ID:AN000573
Instrument Name:Thermo LTQ
Instrument Type:Single quadrupole
MS Type:ESI
Ion Mode:NEGATIVE
  
MS ID:MS000510
Analysis ID:AN000574
Instrument Name:Thermo Trace DSQ
Instrument Type:Single quadrupole
MS Type:EI
Ion Mode:POSITIVE
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