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Zebrafish Cyp1b1 knockout alters eye and brain metabolomic profiles, affecting ocular and neurobehavioral function

ABSTRACT: Zebrafish Cyp1b1 knockout alters eye and brain metabolomic profiles, affecting ocular and neurobehavioral function

PROVIDER: PRJNA1137393 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29884400_1.fastq.gz	Fastqsanger.gz
	SRR29884400_2.fastq.gz	Fastqsanger.gz
	SRR29884401_1.fastq.gz	Fastqsanger.gz
	SRR29884401_2.fastq.gz	Fastqsanger.gz
	SRR29884402_1.fastq.gz	Fastqsanger.gz

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Zebrafish Cyp1b1 knockout alters eye and brain metabolomic profiles, affecting ocular and neurobehavioral function

Project description:Cytochrome P450 1B1 (CYP1B1) is an enzyme that metabolizes endogenous and xenobiotic compounds. CYP1B1 is thought to be involved in the metabolism of compounds vital to the proper development of the eye. Studies have identified CYP1B1 as a causative gene in the ocular disease primary congenital glaucoma (PCG), however CYP1B1’s role in PCG development and related eye disorders is poorly understood. To explore CYP1B1’s role an in vivo zebrafish (Danio rerio) model was used. This study sought to determine if knocking out CYP1B1 produced an ocular defect similar to PCG and whether this could be distinguished from other neurobehavioral effects. To do this a new CYP1B1 knockout line (wh5) was generated using CRISPR/Cas9 induced deletions truncating the protein before the catalytic domain. Behavior assays, untargeted metabolomics, and RNA sequencing was used to determine the phenotype of the wh5 line. RNA sequencing based transcriptomics was performed on adult eye and brain samples. 95 genes in the eye and 45 genes in the brain were found to be differentially expressed between the genotypes. Untargeted metabolomics analysis was performed on the same tissue type and pathway analysis was performed on the separate data sets. KEGG pathways involved in lipid, steroid, amino acid, and nitrogen metabolism were found to be significantly perturbed. A joint pathway multi-omics analysis was performed introducing gene interactions into the metabolomics pathway analysis. wh5 zebrafish performed significantly different in multiple larval and adult behavior assays, however an ocular defect could not be distinguished from other neurobehavioral phenotypes due to large metabolic and transcriptomic changes in both organs.

2025-04-14 | GSE272589 | GEO

Breast cancer cell MCF7+CYP1B1-AS1 LC-MS/MS

Project description:Long non-coding Rnas (lncRNAs) can act as oncogenes or tumor suppressors to regulate cancer development. We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with the prognosis of patients. Lentiviral vectors were used to overexpress CYP1B1-AS1 in MCF7 cells, and the target proteins bound to CYP1B1-AS1 were detected by pulldown assay and mass spectrometry. The function of CYP1B1-AS1 is unknown. Our study revealed the molecular mechanism of CYP1B1-AS1 inhibiting breast cancer proliferation in breast cancer, and provided a new strategy for the treatment of breast cancer targeting lncRNA.

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Project description:Metabolomic analysis on hepatic stellate cells isolated from PBS- or thioacetamide (TAA)-treated wild-type and Cyp1b1 knockout mice was performed to determine the metabolic basis by which CYP1B1 ablation inhibits HSC activation and liver fibrosis.

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ocular microbiota from MGD eye

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Identification of the gene(s) responsible for ocular abnormalities of Hirosaki Small Eye Rat (HiSER)

Project description:HiSER, established in our laboratory, exhibits ocular abnormalities including opacity, lens involution, and retinal detachment. To identify a causative gene(s) of the HiSER phenotype, microarray analysis was performed between HiSER and normal (SDR) eyes. Total RNA was extracted from HiSER and normal (SDR) eyes, and subjected to microarray analysis.

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C57BL6/J livers exposed to low fat and high fat diet, wild-type vs Cyp1b1 null

Project description:Investigating the transcriptional changes in mouse livers exposed to low and high fat diets for 11 weeks. Determine what gene changes in the Cyp1b1 null livers may be contributing to prevention of increased adiposity when givin a high fat diet. Three Comparison experiment. Comparing wild-type low fat vs Cyp1b1 null low fat, wild-type high fat vs Cyp1b1 null high fat and low fat vs high in wild-type mice. Sample size is 3 per group. Limma analysis data provided in Series supplementary file (Normalized log2 ratio of (Cy3/Cy5) representing test group/control group).

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2020-01-31 | E-MTAB-8512 | biostudies-arrayexpress

Epigenome-wide analyis of neurobehavioral variation in preterm infants

Project description:Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in epigenomic measures from buccal cells were associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N=536). We tested whether epigenetic age, age acceleration, or DNA methylation (DNAm) levels at individual loci, measured via the Illumina EPIC microarray, differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications, ranging from most optimal to atypical. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (β1 = 0.201, p-value = 0.026), but no significant difference in age acceleration. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Some of the genes annotated to these CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders. These findings contribute to the existing evidence that neonatal epigenetic variations in buccal cells may be informative for infant neurobehavior.

2019-03-26 | GSE128821 | GEO

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