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
Study ID | ST000352 |
Study Title | Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease |
Study Type | Animal hindbrain comparison |
Study Summary | P15 wildtype mouse hindbrains, P15 twitcher mouse hindbrains, P22 wildtype mouse hindbrains, P22 twitcher mouse hindbrains |
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 |
daesungs@buffalo.edu | |
Phone | 716-881-8980 |
Submit Date | 2016-02-02 |
Num Groups | 4 |
Total Subjects | 32 |
Raw Data Available | Yes |
Raw Data File Type(s) | wiff |
Analysis Type Detail | GC-MS/LC-MS |
Release Date | 2016-03-03 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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: | Mammals |
Factors:
Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)
mb_sample_id | local_sample_id | age | genotype |
---|---|---|---|
SA015419 | UBUF-00099 | P15 | Twitcher |
SA015420 | UBUF-00100 | P15 | Twitcher |
SA015421 | UBUF-00101 | P15 | Twitcher |
SA015422 | UBUF-00102 | P15 | Twitcher |
SA015423 | UBUF-00103 | P15 | Twitcher |
SA015424 | UBUF-00104 | P15 | Twitcher |
SA015425 | UBUF-00105 | P15 | Twitcher |
SA015426 | UBUF-00106 | P15 | Twitcher |
SA015427 | UBUF-00091 | P15 | Wild Type |
SA015428 | UBUF-00092 | P15 | Wild Type |
SA015429 | UBUF-00093 | P15 | Wild Type |
SA015430 | UBUF-00094 | P15 | Wild Type |
SA015431 | UBUF-00095 | P15 | Wild Type |
SA015432 | UBUF-00096 | P15 | Wild Type |
SA015433 | UBUF-00097 | P15 | Wild Type |
SA015434 | UBUF-00098 | P15 | Wild Type |
SA015435 | UBUF-00115 | P22 | Twitcher |
SA015436 | UBUF-00116 | P22 | Twitcher |
SA015437 | UBUF-00117 | P22 | Twitcher |
SA015438 | UBUF-00118 | P22 | Twitcher |
SA015439 | UBUF-00119 | P22 | Twitcher |
SA015440 | UBUF-00120 | P22 | Twitcher |
SA015441 | UBUF-00121 | P22 | Twitcher |
SA015442 | UBUF-00122 | P22 | Twitcher |
SA015443 | UBUF-00107 | P22 | Wild Type |
SA015444 | UBUF-00108 | P22 | Wild Type |
SA015445 | UBUF-00109 | P22 | Wild Type |
SA015446 | UBUF-00110 | P22 | Wild Type |
SA015447 | UBUF-00111 | P22 | Wild Type |
SA015448 | UBUF-00112 | P22 | Wild Type |
SA015449 | UBUF-00113 | P22 | Wild Type |
SA015450 | UBUF-00114 | P22 | 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 | Unspecified | Unspecified | 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: | Unspecified |
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 |
Analysis Protocol File: | pathogenesis_Krabbe_protocol.pdf |
MS ID: | MS000509 |
Analysis ID: | AN000573 |
Instrument Name: | Thermo LTQ |
Instrument Type: | Single quadrupole |
MS Type: | ESI |
Ion Mode: | NEGATIVE |
Analysis Protocol File: | pathogenesis_Krabbe_protocol.pdf |
MS ID: | MS000510 |
Analysis ID: | AN000574 |
Instrument Name: | Thermo Trace DSQ |
Instrument Type: | Single quadrupole |
MS Type: | EI |
Ion Mode: | POSITIVE |
Analysis Protocol File: | pathogenesis_Krabbe_protocol.pdf |