Transcriptome analysis of Dyrk1a-knockin (Ile48LysfsX2) and wild-type mice age of P21 and P60
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ABSTRACT:
PROVIDER: PRJNA1147729 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30249200_1.fastq.gz | Fastqsanger.gz | |||
| SRR30249200_2.fastq.gz | Fastqsanger.gz | |||
| SRR30249201_1.fastq.gz | Fastqsanger.gz | |||
| SRR30249201_2.fastq.gz | Fastqsanger.gz | |||
| SRR30249202_1.fastq.gz | Fastqsanger.gz |
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Project description:Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays, intellectual disability (ID) and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice reportedly leads to ASD-related phenotypes. However, the key pathological mechanisms remain unclear and human DYRK1A mutations remain uncharacterized in mice. Here, we generated and studied Dyrk1a-knockin mice carrying a human ASD patient mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteomic patterns enriched for multiple signaling pathways and synaptic proteins.
2024-12-04 | GSE274730 | GEO
Project description:Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice leads to ASD-related phenotypes, although key pathological mechanisms remain unclear. In addition, human DYRK1A mutations have not been characterized in mice. Here we report Dyrk1a-knockin mice carrying a human mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteome patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues brain volume, behavior, dendrite, synapse, and signaling/synapse phospho-proteome phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to phenotypic alterations in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects of preventing juvenile and adult-stage phenotypes.
2024-12-04 | PXD050100 | Pride
Project description:Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice leads to ASD-related phenotypes, although key pathological mechanisms remain unclear. In addition, human DYRK1A mutations have not been characterized in mice. Here we report Dyrk1a-knockin mice carrying a human mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteome patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues brain volume, behavior, dendrite, synapse, and signaling/synapse phospho-proteome phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to phenotypic alterations in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects of preventing juvenile and adult-stage phenotypes.
2024-07-02 | MSV000095221 | MassIVE
Project description:Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice leads to ASD-related phenotypes, although key pathological mechanisms remain unclear. In addition, human DYRK1A mutations have not been characterized in mice. Here we report Dyrk1a-knockin mice carrying a human mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteome patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues brain volume, behavior, dendrite, synapse, and signaling/synapse phospho-proteome phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to phenotypic alterations in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects of preventing juvenile and adult-stage phenotypes.
2024-12-04 | PXD050102 | Pride
Project description:Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice leads to ASD-related phenotypes, although key pathological mechanisms remain unclear. In addition, human DYRK1A mutations have not been characterized in mice. Here we report Dyrk1a-knockin mice carrying a human mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteome patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues brain volume, behavior, dendrite, synapse, and signaling/synapse phospho-proteome phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to phenotypic alterations in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects of preventing juvenile and adult-stage phenotypes.
2024-02-13 | MSV000094075 | MassIVE
Project description:Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice leads to ASD-related phenotypes, although key pathological mechanisms remain unclear. In addition, human DYRK1A mutations have not been characterized in mice. Here we report Dyrk1a-knockin mice carrying a human mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteome patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues brain volume, behavior, dendrite, synapse, and signaling/synapse phospho-proteome phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to phenotypic alterations in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects of preventing juvenile and adult-stage phenotypes.
2024-02-13 | MSV000094073 | MassIVE
Project description:DYRK1A is a protein kinase with several roles in brain development. This kinase is involved in two intellectual disability syndromes: Down syndrome and DYRK1A haploinsufficiency syndrome. The Dyrk1a+/- mouse is a model for DYRK1A haploinsufficiency syndrome. We used microarray to evaluate the impact of DYRK1A haploinsufficiency in the development of the cerebral cortex.
2019-03-06 | GSE127707 | GEO
Project description:Transcription profiling of transgenic down syndrome mouse model to show the role of DYRK1A gene. The molecular mechanisms that lead to the cognitive defects characteristic of Down syndrome (DS), the most frequent cause of mental retardation, have remained elusive. Here we use a transgenic DS mouse model to show that DYRK1A gene dosage imbalance deregulates chromosomal clusters of genes located near neuron-restrictive silencer factor (REST/NRSF) binding sites. We found that DYRK1A binds the SWI/SNF-complex known to interact with REST/NRSF. Mutation of a REST/NRSF binding site in the promoter of the REST/NRSF target gene L1cam modifies the transcriptional effect of Dyrk1Adosage imbalance on L1cam. DyrkA dosage imbalance perturbs Rest/Nrsf levels with decreased Rest/Nrsf expression in embryonic neurons and increased expression in adult neurons. We identified a coordinated deregulation of multiple genes that are responsible for the cellular phenotypic traits present in DS such as dendritic growth impairment and microcephaly during prenatal cortex development. Dyrk1a overexpression in primary mouse cortical neurons reduced the neuritic complexity. In the postnatal hippocampus, DYRK1A overexpression suppresses a form of synaptic plasticity that may be sufficient to cause DS cognitive defects. We propose that DYRK1A overexpression-related neuronal gene deregulation generates the brain phenotypic changes that characterize DS, with an accessory role for the gene dosage imbalance of other chromosome 21 genes. Transgenic embrionic brain regions versus wild type mice were analysed. The log2 values represent Cy5/Cy3 ratio (transgenic Cy5/wild type Cy3). Each array was scanned under a green laser (543 nm for Cy3 labeling) or a red laser (633 nm for Cy5 labeling) using a ScanArray Lite scanning confocal fuorescent scanner with 10 u resolution (laser power: 85% for Cy5 and 90% for Cy3, gain: 75% for Cy5 and 70% for Cy3). Scanned output files were analyzed using the GenePix Pro 3.0 software. Each spot was defined by automatic positioning of a grid of circles over the image. The average and median pixel intensity ratios calculated from both channels and the local background of each spot were determined. Local background corrected intensity ratios was determined for each spot. The background-corrected expression data were filtered for flagged spots and weak signal. Normalization was performed by the global Lowess method. Studentâs t-test was applied to determine the p value.
2010-05-05 | E-GEOD-14072 | biostudies-arrayexpress
Project description:Transcription profiling of transgenic down syndrome mouse model to show the role of DYRK1A gene. The molecular mechanisms that lead to the cognitive defects characteristic of Down syndrome (DS), the most frequent cause of mental retardation, have remained elusive. Here we use a transgenic DS mouse model to show that DYRK1A gene dosage imbalance deregulates chromosomal clusters of genes located near neuron-restrictive silencer factor (REST/NRSF) binding sites. We found that DYRK1A binds the SWI/SNF-complex known to interact with REST/NRSF. Mutation of a REST/NRSF binding site in the promoter of the REST/NRSF target gene L1cam modifies the transcriptional effect of Dyrk1Adosage imbalance on L1cam. DyrkA dosage imbalance perturbs Rest/Nrsf levels with decreased Rest/Nrsf expression in embryonic neurons and increased expression in adult neurons. We identified a coordinated deregulation of multiple genes that are responsible for the cellular phenotypic traits present in DS such as dendritic growth impairment and microcephaly during prenatal cortex development. Dyrk1a overexpression in primary mouse cortical neurons reduced the neuritic complexity. In the postnatal hippocampus, DYRK1A overexpression suppresses a form of synaptic plasticity that may be sufficient to cause DS cognitive defects. We propose that DYRK1A overexpression-related neuronal gene deregulation generates the brain phenotypic changes that characterize DS, with an accessory role for the gene dosage imbalance of other chromosome 21 genes.
2009-02-23 | GSE14072 | GEO
Project description:Transcriptome analysis of depletion of DYRK1A in HeLa cells Global gene expression profiling has shown upregulation of many genes in the context of DYRK1A depletion in HeLa cells. Many of these genes deregulated by DYRK1A are involved in immune response system. Transcriptome analysis of siRNA against DYRK1A transfected in HeLa cells on GeneChipM-BM-. Human Exon 1.0 ST Arrays (Affimetrix). Control HeLa cells have been transfected with the same concentration of siRNA non-targeting (siNT). Experiment has been done experimental triplicates.
2014-05-01 | E-GEOD-43259 | biostudies-arrayexpress