Dataset Information

TMT mass spectrometry analysis of wild type and Mecp2 null rat CSF of animals aged 23-26 days

ABSTRACT: TMT mass spectrometry analysis of wild type and Mecp2 null rat CSF of animals aged 23-26 days

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Duc Duong

LAB HEAD: Victor Faundez

PROVIDER: PXD029808 | Pride | 2022-10-14

REPOSITORIES: Pride

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Publications

Convergent cerebrospinal fluid proteomes and metabolic ontologies in humans and animal models of Rett syndrome.

Zlatic Stephanie A SA Duong Duc D Gadalla Kamal K E KKE Murage Brenda B Ping Lingyan L Shah Ruth R Fink James J JJ Khwaja Omar O Swanson Lindsay C LC Sahin Mustafa M Rayaprolu Sruti S Kumar Prateek P Rangaraju Srikant S Bird Adrian A Tarquinio Daniel D Carpenter Randall R Cobb Stuart S Faundez Victor V

iScience 20220817 9

MECP2 loss-of-function mutations cause Rett syndrome, a neurodevelopmental disorder resulting from a disrupted brain transcriptome. How these transcriptional defects are decoded into a disease proteome remains unknown. We studied the proteome of Rett cerebrospinal fluid (CSF) to identify consensus Rett proteome and ontologies shared across three species. Rett CSF proteomes enriched proteins annotated to HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, synapse compartments ...[more]

PMID: 36060065

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Project description:A group of postnatal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased MeCP2 dosage causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however, the gene expression changes observed in the hypothalamus and cerebellum of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression. In this study, we compared gene expression changes in the amygdalae of mice lacking MeCP2 (Mecp2-null) and mice overexpressing MeCP2 (MECP2-TG). We chose the amygdala because it is a neuroanatomical region implicated in the control of anxiety and social behavior, two prominent phenotypes in MECP2-TG mice, and hypothesized that transcriptional profiling of this particular brain region may reveal expression changes relevant to heightened anxiety-like behavior and abnormal social behavior. A total of 1,060 genes were altered in opposite directions in both MeCP2 mouse models compared with wild-type littermates, with ~60% up-regulated and ~40% down-regulated. Interestingly, we found a significant enrichment of anxiety- and/or social behavior-related genes among the differentially expressed genes. To determine whether these genes contribute to the anxiety and social behavior phenotypes in MECP2-TG mice, we performed genetic and pharmacologic studies and found that a reduction in Crh suppresses anxiety-like behavior, and a reduction in Oprm1 improves social approach behavior. These studies suggest that MeCP2 impacts molecular pathways involved in anxiety and social behavior, and provide insight into potential therapies for MeCP2 disorders. This study is published in Nature Genetics http://dx.doi.org/10.1038/ng.1066. Total amygdala RNA samples were collected from Mecp2-null male mice (n=4), MECP2-transgenic male mice (n=5), and their wild type male littermates at 6 weeks of age (n=4, n=5 for each group respectively).

Dataset Information

TMT mass spectrometry analysis of wild type and Mecp2 null rat CSF of animals aged 23-26 days

Publications

Convergent cerebrospinal fluid proteomes and metabolic ontologies in humans and animal models of Rett syndrome.

Similar Datasets

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