Summary of Study ST003805
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 PR002379. The data can be accessed directly via it's Project DOI: 10.21228/M84831 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 | ST003805 |
| Study Title | Epigenetic changes, neuronal dysregulation and behavioral abnormalities in Zmym2+/- mutant mice, a genetic animal model of schizophrenia and neurodevelopmental disorders |
| Study Summary | Loss-of-function mutations in ZMYM2 are associated with an increased risk for schizophrenia (SCZ) and neurodevelopmental disorders (NDD). ZMYM2 interacts with proteins that regulate histone modifications and gene expression, but its functions in the brain are unclear. In this multi-omics study, we found that Zmym2 heterozygous knockout in mice leads to widespread disturbance of gene expression and alterations in diverse molecular pathways, including those related to histone modifications and neuronal activity, particularly in neurons. Proteomic analysis of synapses uncovered dysregulation in lipid metabolism and neurofilament pathways. In neurophysiologic and behavioral tests, Zmym2+/- mutant mice exhibit abnormal EEG patterns and locomotor activity. Our findings underscore the critical role of ZMYM2 in brain development and function and establish Zmym2 mutant mice as a useful genetically valid animal model for SCZ and NDD. |
| Institute | Broad Institute of MIT and Harvard |
| Last Name | Mashin |
| First Name | Eivgeni |
| Address | 300 Binney St., Cambridge, Massachusetts, 02142, USA |
| emashin@broadinstitute.org | |
| Phone | 6177147061 |
| Submit Date | 2025-03-14 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-09-15 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002379 |
| Project DOI: | doi: 10.21228/M84831 |
| Project Title: | Epigenetic changes, neuronal dysregulation and behavioral abnormalities in Zmym2+/- mutant mice, a genetic animal model of schizophrenia and neurodevelopmental disorders |
| Project Summary: | Loss-of-function mutations in ZMYM2 are associated with an increased risk for schizophrenia (SCZ) and neurodevelopmental disorders (NDD). ZMYM2 interacts with proteins that regulate histone modifications and gene expression, but its functions in the brain are unclear. In this multi-omics study, we found that Zmym2 heterozygous knockout in mice leads to widespread disturbance of gene expression and alterations in diverse molecular pathways, including those related to histone modifications and neuronal activity, particularly in neurons. Proteomic analysis of synapses uncovered dysregulation in lipid metabolism and neurofilament pathways. In neurophysiologic and behavioral tests, Zmym2+/- mutant mice exhibit abnormal EEG patterns and locomotor activity. Our findings underscore the critical role of ZMYM2 in brain development and function and establish Zmym2 mutant mice as a useful genetically valid animal model for SCZ and NDD. |
| Institute: | Broad Institute |
| Last Name: | Mashin |
| First Name: | Eivgeni |
| Address: | 300 Binney St., Cambridge, Massachusetts, 02142, USA |
| Email: | emashin@broadinstitute.org |
| Phone: | 6177147061 |
| Contributors: | Wei-Chao Huang, Kira A. Perzel Mandell, Sameer Aryal, Bryan J. Song, Antia Valle-Tojeiro, Nathaniel Goble, Chuhan Geng, Ahmet S. Asan, Xiao-Man Liu, Courtney Dennis, Lucas Dailey, Amy Deik, Lucia Inunciaga, Eivgeni Mashin, Zohreh Farsi, Yining Wang, Jen Q. Pan, Clary B. Clish, Hasmik Keshishian, Steven A. Carr, Morgan Sheng |
Subject:
| Subject ID: | SU003939 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | Zmym2+/- mice (C57BL/6NJ-Zmym2em1(IMPC)J /Mmjax; #051239-JAX) |
| Age Or Age Range: | 1-5 Months |
| Gender: | Male and female |
| Animal Animal Supplier: | Jackson Laboratory |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA416627 | 109530_2 | HET |
| SA416628 | 109530_1 | HET |
| SA416629 | 109530_3 | HET |
| SA416630 | 109530_4 | HET |
| SA416631 | 109530_5 | HET |
| SA416632 | 101304_1 | WT |
| SA416633 | 101304_2 | WT |
| SA416634 | 109527_2 | WT |
| SA416635 | 109527_3 | WT |
| SA416636 | 109528_2 | WT |
| Showing results 1 to 10 of 10 |
Collection:
| Collection ID: | CO003932 |
| Collection Summary: | The detailed procedure of brain perfusion and dissection was described previously31. In brief, mice were anesthetized with isoflurane, and transcardial perfusions were performed with ice-cold HBSS (Life Technologies) to remove blood from the brain, which was then immediately frozen in liquid nitrogen vapor and stored at –80°C. Brain dissection was carried out in a cryostat, with all tools precooled to –20°C. The cerebellum was removed first, and then the medial prefrontal cortex, dorsal hippocampus, thalamus, somatosensory cortex, and dorsal striatum, and substantia nigra, were meticulously dissected using biopsy punch and ophthalmic microscalpel in a cryostat (Leica). The brain regions were identified using the Allen Brain Atlas, with each excised tissue stored at –80°C in 1.5 mL tubes. |
| Sample Type: | Brain cortex |
Treatment:
| Treatment ID: | TR003948 |
| Treatment Summary: | NO TREATMENT ADMINISTRED TO THE ANIMALS PRIOR TO SAMPLE COLLECTION |
Sample Preparation:
| Sampleprep ID: | SP003945 |
| Sampleprep Summary: | Brain tissues (n = 5 per genotype) were homogenized using a Qiagen TissueLyser II in water at 1:4 (w:v) (TissueLyser II; Qiagen) and the aqueous homogenate was subjected to protein precipitation. Samples were prepared for each method using extraction procedures that are matched for use with the chromatography conditions: - HILIC-pos: Homogenates (10 μL) samples were extracted with the addition of nine volumes of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic acid containing stable isotope-labeled internal standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope Laboratories). The samples were centrifuged (10 min, 9,000g, 4°C), and the supernatants (10 μL) injected directly onto column. - C8-pos: Homogenates (10 μL) were extracted using 190 μL isopropanol containing 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine as an internal standard (Avanti Polar Lipids; Alabaster, AL). After centrifugation (10 min, 9,000g, ambient temperature), supernatants (2 μl) were injected directly onto column. - C18-neg: Homogenates (30 μL) were extracted using 90 μl methanol containing 15R-15-methyl ProstaglandinA2,15R-15-methyl ProstaglandinF2α, 15S-15-methyl ProstaglandinD2, 15S-15-methyl Prostaglandin E1, and 15S-15-methyl Prostaglandin E2 as internal standards (Cayman Chemical Co.) and centrifuged (10 min, 9,000g, 4°C). The supernatants (10 μL) were injected onto column. - HILIC-neg: Homogenates (30 μL) were extracted with the addition of four volumes of 80% methanol containing inosine-15N4, thymine-d4 and glycocholate-d4 internal standards (Cambridge Isotope Laboratories). The samples were centrifuged (10 min, 9,000g, 4°C) and the supernatants 10 μL) were injected directly onto column. |
Chromatography:
| Chromatography ID: | CH004743 |
| Instrument Name: | Shimadzu Nexera X2 |
| Column Name: | Waters Atlantis HILIC Silica (150 x 2.1 mm, 3 µm) |
| Column Temperature: | 30℃ |
| Flow Gradient: | Isocratically with 5% mobile phase A for 1 minute followed by a linear gradient to 40% mobile phase B over 10 minutes |
| Flow Rate: | 250 µL/min |
| Solvent A: | 100% Water; 10 mM Ammonium Formate; 0.1% Formic Acid |
| Solvent B: | 100% Acetonitrile; 0.1% Formic Acid |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH004744 |
| Instrument Name: | Shimadzu Nexera X2 |
| Column Name: | Waters ACQUITY UPLC BEH C8 (100 x 2.1 mm, 1.7 µm) |
| Column Temperature: | 40℃ |
| Flow Gradient: | The column was eluted at a flow rate of 450 µL/min isocratically for 1 minute at 80% mobile phase A, followed by a linear gradient to 80% mobile-phase B over 2 minutes, a linear gradient to 100% mobile phase B over 7 minutes, and then 3 minutes at 100% mobile-phase B. |
| Flow Rate: | 450 µL/min |
| Solvent A: | 95% Water/5% Methanol; 10 mM Ammonium acetate; 0.1% Acetic acid |
| Solvent B: | 100% Methanol; 0.1% Acetic acid |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004745 |
| Instrument Name: | Shimadzu Nexera X2 |
| Column Name: | Phenomenex Luna NH2 (150 x 2.1 mm, 3 µm) |
| Column Temperature: | 30℃ |
| Flow Gradient: | The column was eluted with initial conditions of 10% mobile phase A and 90% mobile phase B followed by a 10 min linear gradient to 100% mobile phase A. |
| Flow Rate: | 400 µL/min |
| Solvent A: | 100% water; 20 mM ammonium acetate; 20 mM ammonium hydroxide |
| Solvent B: | 75% acetonitrile/25% methanol; 10 mM ammonium hydroxide |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH004746 |
| Instrument Name: | Shimadzu Nexera X2 |
| Column Name: | Waters ACQUITY UPLC HSS T3 (150 x 2.1 mm, 1.8 µm) |
| Column Temperature: | 45℃ |
| Flow Gradient: | The column was eluted isocratically at a flow rate of 450 µL/min with 20% mobile phase A for 3 minutes followed by a linear gradient to 100% mobile phase B over 12 minutes. |
| Flow Rate: | 450 µL/min |
| Solvent A: | 100% water; 0.01% formic acid |
| Solvent B: | 100% acetonitrile; 0.01% acetic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006254 |
| Analysis Type: | MS |
| Chromatography ID: | CH004743 |
| Num Factors: | 2 |
| Num Metabolites: | 329 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003805_AN006254_Results.txt |
| Units: | abundances |
| Analysis ID: | AN006255 |
| Analysis Type: | MS |
| Chromatography ID: | CH004744 |
| Num Factors: | 2 |
| Num Metabolites: | 390 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003805_AN006255_Results.txt |
| Units: | abundances |
| Analysis ID: | AN006256 |
| Analysis Type: | MS |
| Chromatography ID: | CH004745 |
| Num Factors: | 2 |
| Num Metabolites: | 82 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003805_AN006256_Results.txt |
| Units: | abundances |
| Analysis ID: | AN006257 |
| Analysis Type: | MS |
| Chromatography ID: | CH004746 |
| Num Factors: | 2 |
| Num Metabolites: | 82 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003805_AN006257_Results.txt |
| Units: | abundances |
