Unraveling autophagic imbalances and therapeutic insights in Mecp2-deficient models
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1133812 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29759947_1.fastq.gz | Fastqsanger.gz | |||
| SRR29759947_2.fastq.gz | Fastqsanger.gz | |||
| SRR29759948_1.fastq.gz | Fastqsanger.gz | |||
| SRR29759948_2.fastq.gz | Fastqsanger.gz | |||
| SRR29759949_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:Loss of function mutations in MECP2are associated to Rett syndrome (RTT), a severe neurodevelopmental disease. Mainly working as a transcriptional regulator, MECP2 absence leads to gene expression perturbations resulting in deficits of synaptic function and neuronal activity. In addition, RTT patients and mouse models suffer from a complex metabolic syndrome, suggesting that related cellular pathways might contribute to neuropathogenesis. Along this line, autophagy is critical in sustaining developing neuron homeostasis by breaking down dysfunctional proteins, lipids, and organelles. Here, we investigated the autophagic pathway in RTT and found reduced content of autophagic vacuoles in Mecp2 knock-out neurons. This correlates with defective lipidation of LC3B-II probably caused by a deficiency of the autophagic membrane lipid phosphatidylethanolamine. The administration of the autophagy inducer trehalose recovers LC3B lipidation, autophagosomes content in knock-out neurons, and ameliorates their morphology, neuronal activity and synaptic ultrastructure. Moreover, we provide evidence for attenuation of motor and exploratory impairment in Mecp2 knock-out mice upon trehalose administration. Overall, our findings open new perspectives for neurodevelopmental disorders therapies based on the concept of autophagy modulation.
2024-08-26 | GSE271893 | GEO
Project description:Loss-of-function mutations in MeCP2 are associated to Rett syndrome (RTT), a severe neurodevelopmental disease. Mainly working as a transcriptional regulator, MeCP2 absence leads to gene expression perturbations resulting in deficits of synaptic function and neuronal activity. In addition, RTT patients and mouse models suffer from a complex metabolic syndrome, suggesting that related cellular pathways might contribute to neuropathogenesis. Along this line, autophagy is critical in sustaining developing neuron homeostasis by breaking down dysfunctional proteins, lipids, and organelles. Here, we investigated the autophagic pathway in RTT and found reduced content of autophagic vacuoles in Mecp2 knock-out neurons. This correlates with defective lipidation of LC3B, probably caused by a deficiency of the autophagic membrane lipid phosphatidylethanolamine. The administration of the autophagy inducer trehalose recovers LC3B lipidation, autophagosomes content in knock-out neurons, and ameliorates their morphology, neuronal activity and synaptic ultrastructure. Moreover, we provide evidence for attenuation of motor and exploratory impairment in Mecp2 knock-out mice upon trehalose administration. Overall, our findings open new perspectives for neurodevelopmental disorders therapies based on the concept of autophagy modulation.
| S-SCDT-10_1038-S44321-024-00151-W | biostudies-other
Project description:Loss-of-function mutations in MECP2 are associated to Rett syndrome (RTT), a severe neurodevelopmental disease. Mainly working as a transcriptional regulator, MeCP2 absence leads to gene expression perturbations resulting in deficits of synaptic function and neuronal activity. In addition, RTT patients and mouse models suffer from a complex metabolic syndrome, suggesting that related cellular pathways might contribute to neuropathogenesis. Along this line, autophagy is critical in sustaining developing neuron homeostasis by breaking down dysfunctional proteins, lipids, and organelles.Here, we investigated the autophagic pathway in RTT and found reduced content of autophagic vacuoles in Mecp2 knock-out neurons. This correlates with defective lipidation of LC3B, probably caused by a deficiency of the autophagic membrane lipid phosphatidylethanolamine. The administration of the autophagy inducer trehalose recovers LC3B lipidation, autophagosomes content in knock-out neurons, and ameliorates their morphology, neuronal activity and synaptic ultrastructure. Moreover, we provide evidence for attenuation of motor and exploratory impairment in Mecp2 knock-out mice upon trehalose administration. Overall, our findings open new perspectives for neurodevelopmental disorders therapies based on the concept of autophagy modulation.
| S-EPMC11555085 | biostudies-literature
Project description:Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome that is one of the most frequent sources of intellectual disability in women. It has been shown that mutant astrocytes contribute to neuronal defects, probably as a result of aberrant secretion of soluble factor(s). Based on the hypothesis that this irregular secretion of soluble factor is the result of abnormal transcription of those factors, we have compared the gene expression profiles of wild type and mutant astrocytes from Mecp2 308/y mice by using Affymetrix mouse 2.0 microarrays. P0 newborns from pregnant Mecp2 308/+ heterozygous mice were used for the preparation of dissociated cortical astrocyte cultures. Four wild-type and four mutant confluent astrocytes cultures were used for total RNA extraction with the Qiagen RNeasy kit (Qiagen, Courtaboeuf, France) as described by the manufacturer. The gene expression profiles of wild type and mutant astrocytes from Mecp2 308/y mice have been assayed by using Affymetrix mouse 2.0 microarrays.
2015-01-01 | E-GEOD-56709 | biostudies-arrayexpress
Project description:Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome that is one of the most frequent sources of intellectual disability in women. It has been shown that mutant astrocytes contribute to neuronal defects, probably as a result of aberrant secretion of soluble factor(s). Based on the hypothesis that this irregular secretion of soluble factor is the result of abnormal transcription of those factors, we have compared the gene expression profiles of wild type and mutant astrocytes from Mecp2 308/y mice by using Affymetrix mouse 2.0 microarrays.
2015-01-01 | GSE56709 | GEO
Project description:MECP2-R270X transgenic mice (TG) and MECP2-G273X TG mice were generated in the Zoghbi Lab. These mice express the respective truncated form of MeCP2 tagged with GFP at the C-terminus from a transgenic human PAC containing all known regulatory sequences. These transgenes were maintained on a wild-type pure FVB background. For experiments each transgenic line was crossed by Mecp2 null mice (Mecp2 tm1.1Bird) on a pure 129SvEv background and the resulting male F1 hybrid progeny (FVB;129SvEv) that lacked endogenous MeCP2 expression but expressed either transgene (Mecp2 -/y; MECP2-R270X TG or Mecp2-/y; MECP2-G273X TG) were used for ChIP-Seq analysis. Whole brain from either the R270X mice (Mecp2 -/y; MECP2-R270X TG) or the G273X mice (Mecp2 -/y; MECP2-G273X TG) was formaldehyde crosslinked and purified chromatin was immunoprecipitated with anti-GFP antibody (Abcam ab6556). 2 samples: R270X (Mecp2 -/y; MECP2-R270X TG) and G273X (Mecp2 -/y; MECP2-G273X TG) both on an F1 (FVB;129SvEv) hybrid background
2013-03-12 | E-GEOD-36536 | biostudies-arrayexpress
Project description:MeCP2 globally regulates gene expression in the brain. One example is Growth-differentiation factor 11 (Gdf11), which is down-regulated upon loss of MeCP2 and up-regulated upon gain of MeCP2. To assess if MeCP2 binds near the Gdf11 locus we performed CUT&RUN for MeCP2 in Mecp2-knockout or MECP2-transgenic hippocampus. To assess if a repressive histone modification (H3K27me3) was concordantly changed we profiled H3k27me3 in these same matched tissues.
2023-02-23 | GSE213752 | GEO
Project description:MECP2-R270X transgenic mice (TG) and MECP2-G273X TG mice were generated in the Zoghbi Lab. These mice express the respective truncated form of MeCP2 tagged with GFP at the C-terminus from a transgenic human PAC containing all known regulatory sequences. These transgenes were maintained on a wild-type pure FVB background. For experiments each transgenic line was crossed by Mecp2 null mice (Mecp2 tm1.1Bird) on a pure 129SvEv background and the resulting male F1 hybrid progeny (FVB;129SvEv) that lacked endogenous MeCP2 expression but expressed either transgene (Mecp2 -/y; MECP2-R270X TG or Mecp2-/y; MECP2-G273X TG) were used for ChIP-Seq analysis. Whole brain from either the R270X mice (Mecp2 -/y; MECP2-R270X TG) or the G273X mice (Mecp2 -/y; MECP2-G273X TG) was formaldehyde crosslinked and purified chromatin was immunoprecipitated with anti-GFP antibody (Abcam ab6556).
2013-03-12 | GSE36536 | GEO
Project description:Investigation of whole genome gene expression level changes in mecp2 morphant zebrafish embryos as compared to wild-type strain.
2015-07-21 | GSE71173 | GEO
Project description:MeCP2 and H3K27me3 binding in Mecp2-knockout and MECP2-transgenic hippocampus
| PRJNA882406 | ENA