RNAseq data for FACS sorted glial cells KPNA4 KO mice for Importin α4 deficiency induces psychiatric disorder-related behavioral deficits and neuroinflammation in mice.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101403 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28714421_1.fastq.gz | Fastqsanger.gz | |||
| SRR28714421_2.fastq.gz | Fastqsanger.gz | |||
| SRR28714422_1.fastq.gz | Fastqsanger.gz | |||
| SRR28714422_2.fastq.gz | Fastqsanger.gz | |||
| SRR28714423_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Importin α4, which is encoded by the Kpna4 gene, is a well characterized nuclear-cytoplasmic transport factor known to mediate transport of transcription factors including NF-κB. Here, we report that Kpna4 knock-out (KO) mice exhibit psychiatric disorder-related behavioral abnormalities such as anxiety-related behaviors, deceased social interaction and sensorimotor gating deficits. Contrary to a previous study predicting attenuated NF-κB activity as a result of Kpna4 deficiency, we observed a significant increase in expression levels of NF-κB genes and pro-inflammatory cytokines such as TNFα, Il1β or Il-6 in the Prefrontal Cortex or Basolateral Amygdala of the KO mice. Moreover, examination of inflammatory responses in primary cells revealed that Kpna4 deficient cells have an increased inflammatory response, which was rescued by addition of not only full-length, but also a nuclear transport deficient truncation mutant of importin α4, suggesting contribution of its non-transport functions. Furthermore, RNAseq of sorted adult Microglia and Astrocytes and subsequent transcription factor analysis suggested increases in Polycomb repressor complex 2 (PRC2) activity in Kpna4 KO cells. Taken together, importin α4 deficiency induces psychiatric disorder-related behavioral deficits in mice, along with an increased inflammatory response and possible alteration of PRC2 activity in glial cells.
2024-04-18 | GSE264180 | GEO
Project description:Spermatogenesis, a fundamental process in male reproduction, is driven by an ordered series of events, which rely on the trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin α7 (Kpna6) in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells culminating in oligozoospermia. Importin α7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells from the seminiferous epithelium and a compromised nuclear transport of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis that are accompanied by a disturbed histone-protamine-exchange in elongating spermatids, resulting in incomplete sperm maturation and a massive loss of sperms. Our work uncovers the essential role of importin α7 in spermatogenesis and hence in male fertility.
2021-09-20 | GSE160969 | GEO
Project description:To test whether nuclear importin alpha2 can regulate transcription, we sought to examine gene expression changes in cells with nuclear accumulation of importin alpha2 by performing microarray analysis. We designed an experiment in which EGFP-fused full-length importin alpha2 was transfected into HeLa cells. To exclude the possibility that exogenous, full-length importin alpha2 protein enhances nuclear transport of karyophilic proteins such as transcription factors and thereby directly influences gene expression, a mutant of importin alpha2 which is mutated in the C-terminal CAS-binding domain was also transfected, so that it is never recycled to the cytoplasm and shows complete nuclear localization. We undertook to investigate whether there were changes in gene expression common to cells expressing the full-length importin alpha2 and the C-terminal mutant (C-mutant) isoform. EGFP vs. EGFP-importin alpha2 full length, or EGFP vs EGFP-importin alpha2 CAS-binding mutant. One replicate each. EGFP-expressing cells are used as a control.
2010-11-24 | E-GEOD-25303 | biostudies-arrayexpress
Project description:Introduction: The mechanisms governing synaptonuclear transport, and the transcriptional pathways that are at the core of neuronal disorders are poorly understood. The importin family of nuclear import factors has pivotal roles in such pathways, due to their involvement in intracellular transport from both synapse to soma and cytoplasm to nucleus. Mammals express six different isoforms of importin α, which bind an Importin β to form transport complexes for specific cargoes. Methods: We addressed the roles of importin α isoforms in mammalian CNS by evaluation of a systematic series of importin α knockout mice. A comprehensive battery of behavioral tests was used to investigate spontaneous and novelty-induced locomotion, basal ganglia function, motor coordination, neuromuscular integration, anxiety-related behaviors and memory. Subsequent analyses using acute-brain slice electrophysiology, RNA-seq, bioinformatics, imaging and pharmacology was used in order to delineate the contribution of genes and signaling pathways involved in the identified phenotype and screen for new therapeutic approaches. Results and Discussion: During the course of comprehensive behavioral profiling of importin α mouse mutants, we identified an importin α knockout (KO) mouse with significantly reduced anxiety levels. Electrophysiological recordings in acute hippocampal slices showed a reduced short-term and presynaptic plasticity (paired-pulse facilitation deficit, lower PTP), while LTP was not affected in these mutants. We then performed transcriptional profiling (RNA-seq) from hippocampal extracts of wild type versus mutant animals after exposure to an anxiogenic drug. Computational analysis revealed differences in the expression of genes and the involvement of transcription factors. Drugs that activate LXR or the Sphingosine 1 phosphate receptor have robust anxiolytic effects, while a Sphk1 blocker reverses anxiolysis in the importin α5 knockout mouse. Thus, importin α5 influences anxiety by regulating nuclear import in neurons.
2018-11-22 | GSE106546 | GEO
Project description:Here we show that importin alpha (α) 3 (KPNA4) controls pain responsiveness in peripheral sensory neurons. An importin α3 knockout mouse showed reduced responsiveness to noxious heat or chemical pain, as well as greater tolerance to neuropathic pain. Similar findings were obtained upon acute knockdown of importin α3 in peripheral sensory neurons. Transcriptome analyses and immunohistochemistry indicated that importin α 3 deficient neurons were impaired in nuclear import of c-Fos. Forty days after spared nerve injury acute down-regulation of importin α3, c-FOS, Jun and the dominat negative AAV9 viruses rescue the neuropathic pain phenotype. In silico screens identified importin α3 deficiency mimicking drug leads that attenuated neuropathic pain and reduced c-Fos nuclear localization. Hence, perturbing c-Fos nuclear import by importin α3 can provide analgesia at peripheral loci in the nervous system
2020-08-17 | GSE137515 | GEO
Project description:Methylglyoxal (MG) is a reactive alpha-dicarbonyl by-product of glycolysis. Several bio-defense systems to detoxify the highly toxic MG are equipped in our body, including an enzymatic system by glyoxalase (GLO) 1 and GLO2 and a scavenge system by vitamin B6 (VB6). We have reported that some population of patients with schizophrenia shows impairment of the MG detoxification systems. Although we have evidences showing a link between impairment of MG detoxification systems and development of schizophrenia, the molecular mechanism to connect them remains poorly understood. Here, we generated a novel mouse model for MG detoxification deficits by feeding Glo1 knockout mice with VB6-lacking diets (KO/VB6(-)), and evaluate effects of impaired MG detoxification systems on brain function. KO/VB6(-) mice showed the accumulation of MG in the prefrontal cortex (PFC), hippocampus, and striatum, and displayed schizophrenia-like behavioral deficits, such as social deficits, cognitive impairment, a sensorimotor deficit in the prepulse inhibition test. Furthermore, we found aberrant gene expression related to mitochondria function in the PFC of the KO/VB6(-) mice by RNA-seq and weighted gene correlation network analysis (WGCNA). Finally, we actually demonstrated respiratory deficits in mitochondria isolated from the PFC of KO/VB6(-) mice. These findings suggest that MG detoxification deficits might cause schizophrenia-like behavioral deficits via mitochondrial dysfunction in the PFC.
2021-07-20 | GSE149585 | GEO
Project description:To test whether nuclear importin alpha2 can regulate transcription, we sought to examine gene expression changes in cells with nuclear accumulation of importin alpha2 by performing microarray analysis. We designed an experiment in which EGFP-fused full-length importin alpha2 was transfected into HeLa cells. To exclude the possibility that exogenous, full-length importin alpha2 protein enhances nuclear transport of karyophilic proteins such as transcription factors and thereby directly influences gene expression, a mutant of importin alpha2 which is mutated in the C-terminal CAS-binding domain was also transfected, so that it is never recycled to the cytoplasm and shows complete nuclear localization. We undertook to investigate whether there were changes in gene expression common to cells expressing the full-length importin alpha2 and the C-terminal mutant (C-mutant) isoform.
2010-11-24 | GSE25303 | GEO
Project description:Mice modeling human CNVs associated with psychiatric disorders
| PRJNA533098 | ENA
Project description:Gut Microbiota from Human Autism Spectrum Disorder Induces Behavioral Deficits in Mice
| PRJNA432094 | ENA
Project description:Deciphering the role of importin alpha in mammalian central neurons - Hippocampal gene expression profiling in importin alpha5-deleted mice
| PRJNA417195 | ENA