Analysis of behavior using genetical genomics in mice as a model: from alcohol preferences to gene expression differences

Genome ◽  
2007 ◽  
Vol 50 (10) ◽  
pp. 877-897 ◽  
Author(s):  
Shiva M. Singh ◽  
Julie Treadwell ◽  
Morgan L. Kleiber ◽  
Michelle Harrison ◽  
Raihan K. Uddin
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Human Subjects ◽  
Fold Increase ◽  
Global Gene Expression ◽  
Genetic Dissection ◽  
Behavioral Phenotypes ◽  
Neurotransmitter Transport ◽  
Genetic Strains ◽  
Different Strains

Most familial behavioral phenotypes result from the complex interaction of multiple genes. Studies of such phenotypes involving human subjects are often inconclusive owing to complexity of causation and experimental limitations. Studies of animal models argue for the use of established genetic strains as a powerful tool for genetic dissection of behavioral disorders and have led to the identification of rare genes and genetic mechanisms implicated in such phenotypes. We have used microarrays to study global gene expression in adult brains of four genetic strains of mice (C57BL/6J, DBA/2J, A/J, and BALB/c). Our results demonstrate that different strains show expression differences for a number of genes in the brain, and that closely related strains have similar patterns of gene expression as compared with distantly related strains. In addition, among the 24 000 genes and ESTs on the microarray, 77 showed at least a 1.5-fold increase in the brains of C57BL/6J mice as compared with those of DBA/2J mice. These genes fall into such functional categories as gene regulation, metabolism, cell signaling, neurotransmitter transport, and DNA/RNA binding. The importance of these findings as a novel genetic resource and their use and application in the genetic analysis of complex behavioral phenotypes, susceptibilities, and responses to drugs and chemicals are discussed.

Gene Expression Profiling of Adenosine Signaling in the Human Monocytic THP-1 Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3886-3886
Author(s):  
Chin-Fu Chen ◽  
Chun-Huai Cheng
Keyword(s):  
Gene Expression ◽  
Cytokine Production ◽  
Mrna Level ◽  
Glutamate Transporter ◽  
Fold Increase ◽  
Global Gene Expression ◽  
Organ Damage ◽  
Rna Modification ◽  
Signal Transducers ◽  
Anti Inflammatory

Abstract Inflammation, a host response to infection or injury, is usually beneficial to the host. However, uncontrolled or prolonged inflammation can cause tissue and organ damage, and possibly lead to diseases like atherosclerosis, rheumatoid arthritis, asthma, and cancers. Much attention has focused on pro-inflammatory signaling but little is known about the mechanisms that resolve inflammation (anti-inflammation). Adenosine, released from leukocytes and endothelial cells, is an endogenous anti-inflammatory mediator that down-regulates acute inflammation in part by modulating macrophage cytokine production. LPS (lipopolysaccharide) is a potent pro-inflammatory reagent of macrophages that acts primarily through Toll-like receptors (TLRs). Studies using murine cells have showed that co-stimulation of both adenosine receptors and TLRs greatly increases the production of vascular endothelial growth factor (VEGF). The mechanisms for this synergistic interaction are currently not known. It is also unknown whether the adenosine-LPS interaction occurs in human macrophages. To gain insights and to generate new hypotheses, we have utilized oligonucleotide microarrays to examine how adenosine alters global gene expression in the human monocytic THP-1 cell line. We analyzed differentially expressed genes induced by adenosine alone, by LPS alone, and by adenosine in the presence of LPS. The genes activated by adenosine are enriched in processes transcription, RNA modification and cellular defense response, but are lacking processes involved in lipid biosynthesis and protein catabolism. Our result shows that at the mRNA level adenosine alone induces a nine-fold increase of VEGF, and adenosine in the presence of LPS elevates VEGF expression three fold when compared to controls. Many genes with the greatest induction by adenosine in the presence of LPS have unknown functions in macrophages. The genes with known functions include transcription regulation (EGR1, HEY1, and CTBP1), nuclear receptors (NR4A2), immune response modulators (IL1A, STAT4, and INHBA), apoptosis facilitator (BCL2L11), signal transducers (PRPF4B, LNK, and ARHGEF7), and glutamate transporter (SLC1A2). These results suggest that the mechanisms by which adenosine mediates its anti-inflammatory signals are far more complex than simply regulating cytokine production. In addition, we found that three TLR signaling genes are uniquely suppressed by adenosine in the presence of LPS: CREB1, TLR1, and IRF2. CREB1 modulates transcription of cAMP signaling; TLR1 is part of the TLR2/TLR1 complex and can regulate TLR2 mediated pathways; IRF2 is a mediator of interferon signaling. We are in the process of verifying these observations using real-time PCR and independent RNA samples.

scholarly journals Overexpression of the RNA-binding protein NrdA affects global gene expression and secondary metabolism inAspergillusspecies

2021 ◽  
Author(s):  
Chihiro Kadooka ◽  
Kosuke Izumitsu ◽  
Teigo Asai ◽  
Kazuki Mori ◽  
Kayu Okutsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Secondary Metabolites ◽  
Aspergillus Fumigatus ◽  
Mrna Expression ◽  
Secondary Metabolism ◽  
Aspergillus Nidulans ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Global Gene Expression

ABSTRACTRNA-binding protein Nrd1 plays a role in RNA polymerase II transcription termination. In this study, we showed that the orthologous NrdA is important in global mRNA expression and secondary metabolism inAspergillusspecies. We constructed annrdAconditional expression strain using the Tet-On system inAspergillus luchuenesismut.kawachii. Downregulation ofnrdAcaused a severe growth defect, indicating that NrdA is essential for the proliferation ofA. kawachii. Parallel RNA-sequencing and RNA immunoprecipitation-sequencing analysis identified potential NrdA-interacting transcripts, corresponding to 32% of the predicted protein coding genes ofA. kawachii. Subsequent gene ontology analysis suggested that overexpression of NrdA affects the production of secondary metabolites. To clarify this, we constructed NrdA-overexpressing strains ofAspergillus nidulans,Aspergillus fumigatus, andAspergillus oryzae. Overexpression of NrdA reduced the production of sterigmatocystin and penicillin inA. nidulans, as well as that of helvolic acid and pyripyropene A inA. fumigatus. Moreover, it increased the production of kojic acid and reduced production of penicillin inA. oryzae. These effects were accompanied by almost consistent transcriptional changes in the relevant genes. Collectively, these results suggest that NrdA is the essential RNA-binding protein, which plays a significant role in global gene expression and secondary metabolism inAspergillusspecies.IMPORTANCENrd1, a component of the Nrd1–Nab3–Sen1 complex, is an essential RNA-binding protein involved in transcriptional termination in yeast. However, its role in filamentous fungi has not been studied. In this study, we characterized an orthologous NrdA in theAspergillusspecies, identified potential NrdA-interacting mRNA, and investigated the effect of overexpression of NrdA on mRNA expression inAspergillus luchuensismut.kawachii. The results indicated that NrdA controls global gene expression involved in versatile metabolic pathways, including the secondary metabolic process. We demonstrated that NrdA overexpression significantly affected the production of secondary metabolites inAspergillus nidulans,Aspergillus oryzae, andAspergillus fumigatus. Our findings are of importance to the fungal research community because the secondary metabolism is an industrially and clinically important aspect for theAspergillusspecies.

scholarly journals Analysis of fibroblasts from patients with cblC and cblG genetic defects of cobalamin metabolism reveals global dysregulation of alternative splicing

2020 ◽  
Vol 29 (12) ◽  
pp. 1969-1985
Author(s):  
Charif Rashka ◽  
Sébastien Hergalant ◽  
Natacha Dreumont ◽  
Abderrahim Oussalah ◽  
Jean-Michel Camadro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Wide Spectrum ◽  
Global Gene Expression ◽  
Genetic Defects ◽  
Inherited Disorders ◽  
Cytoskeleton Organization ◽  
Transcript Processing ◽  
Potential Strategy

ABSTRACT Vitamin B12 or cobalamin (Cbl) metabolism can be affected by genetic defects leading to defective activity of either methylmalonyl-CoA mutase or methionine synthase or both enzymes. Patients usually present with a wide spectrum of pathologies suggesting that various cellular processes could be affected by modifications in gene expression. We have previously demonstrated that these genetic defects are associated with subcellular mislocalization of RNA-binding proteins (RBP) and subsequent altered nucleo-cytoplasmic shuttling of mRNAs. In order to characterize the possible changes of gene expression in these diseases, we have investigated global gene expression in fibroblasts from patients with cblC and cblG inherited disorders by RNA-seq. The most differentially expressed genes are strongly associated with developmental processes, neurological, ophthalmologic and cardiovascular diseases. These associations are consistent with the clinical presentation of cblC and cblG disorders. Multivariate analysis of transcript processing revaled splicing alterations that led to dramatic changes in cytoskeleton organization, response to stress, methylation of macromolecules and RNA binding. The RNA motifs associated with this differential splicing reflected a potential role of RBP such as HuR and HNRNPL. Proteomic analysis confirmed that mRNA processing was significantly disturbed. This study reports a dramatic alteration of gene expression in fibroblasts of patients with cblC and cblG disorders, which resulted partly from disturbed function of RBP. These data suggest to evaluate the rescue of the mislocalization of RBP as a potential strategy in the treatment of severe cases who are resistant to classical treatments with co-enzyme supplements.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

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