Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart

We have used mouse 27k cDNA arrays to compare gene expression patterns in four sets of three hearts each of neonatal wild types and four sets of three hearts each of littermates lacking the major cardiac gap junction protein, connexin43 (Cx43). Each individual set of hearts was hybridized against aliquots of an RNA standard prepared from selected mouse tissues, allowing calculation of variability and coordination of gene expression among the samples from both genotypes. Overall variance of gene expression was found to be markedly higher in wild-type hearts than in those from Cx43 null littermates. Expression levels of 586 of 5,613 adequately quantifiable distinct genes with known protein products were statistically altered in the Cx43 null hearts, 38 upregulated and 548 downregulated compared with wild types. Downregulation was confirmed for seven tested genes by quantitative RT-PCR. Functions of proteins encoded by the altered genes encompassed all functional categories, with largest percent changes in genes involved in intracellular transport and transcription factors. Among the downregulated genes in the Cx43 null hearts were those related to neuronal and glial function, suggesting that cardiac innervation might be compromised as a consequence of Cx43 deletion. This was supported by immunodetection of sympathetic innervation, using antibodies to the synaptic vesicle protein synaptophysin and to the adrenergic nerve terminal marker tyrosine hydroxylase. These findings reinforce the proposal that the cardiac abnormality in Cx43 null animals may be contributed by altered innervation and indicate that Cx43 deletion has consequences in addition to reduced intercellular communication.

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Expression Patterns in Reductive Iron Assimilation and Functional Consequences during Phagocytosis of Lichtheimia corymbifera, an Emerging Cause of Mucormycosis

Journal of Fungi ◽

10.3390/jof7040272 ◽

2021 ◽

Vol 7 (4) ◽

pp. 272

Author(s):

Felicia Adelina Stanford ◽

Nina Matthias ◽

Zoltán Cseresnyés ◽

Marc Thilo Figge ◽

Mohamed I. Abdelwahab Hassan ◽

...

Keyword(s):

Gene Expression ◽

Iron Uptake ◽

Intracellular Transport ◽

Pathogenic Fungus ◽

Expression Patterns ◽

Iron Depletion ◽

Iron Assimilation ◽

Human Pathogenic Fungus ◽

Hyphal Formation ◽

Yeast Mutants

Iron is an essential micronutrient for most organisms and fungi are no exception. Iron uptake by fungi is facilitated by receptor-mediated internalization of siderophores, heme and reductive iron assimilation (RIA). The RIA employs three protein groups: (i) the ferric reductases (Fre5 proteins), (ii) the multicopper ferroxidases (Fet3) and (iii) the high-affinity iron permeases (Ftr1). Phenotyping under different iron concentrations revealed detrimental effects on spore swelling and hyphal formation under iron depletion, but yeast-like morphology under iron excess. Since access to iron is limited during pathogenesis, pathogens are placed under stress due to nutrient limitations. To combat this, gene duplication and differential gene expression of key iron uptake genes are utilized to acquire iron against the deleterious effects of iron depletion. In the genome of the human pathogenic fungus L. corymbifera, three, four and three copies were identified for FRE5, FTR1 and FET3 genes, respectively. As in other fungi, FET3 and FTR1 are syntenic and co-expressed in L. corymbifera. Expression of FRE5, FTR1 and FET3 genes is highly up-regulated during iron limitation (Fe-), but lower during iron excess (Fe+). Fe- dependent upregulation of gene expression takes place in LcFRE5 II and III, LcFTR1 I and II, as well as LcFET3 I and II suggesting a functional role in pathogenesis. The syntenic LcFTR1 I–LcFET3 I gene pair is co-expressed during germination, whereas LcFTR1 II- LcFET3 II is co-expressed during hyphal proliferation. LcFTR1 I, II and IV were overexpressed in Saccharomyces cerevisiae to represent high and moderate expression of intracellular transport of Fe3+, respectively. Challenge of macrophages with the yeast mutants revealed no obvious role for LcFTR1 I, but possible functions of LcFTR1 II and IVs in recognition by macrophages. RIA expression pattern was used for a new model of interaction between L. corymbifera and macrophages.

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Regional heterogeneity in rat Peyer’s patches through whole transcriptome analysis

Experimental Biology and Medicine ◽

10.1177/1535370220973014 ◽

2020 ◽

pp. 153537022097301

Author(s):

Charles L Phillips ◽

Bradley A Welch ◽

Michael R Garrett ◽

Bernadette E Grayson

Keyword(s):

Gene Expression ◽

Small Intestine ◽

Transcriptome Analysis ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Peyer's Patches ◽

Peyer’S Patches ◽

Junction Protein ◽

Whole Transcriptome Analysis ◽

Whole Transcriptome

Peyer’s patches are gut-associated lymphoid tissue located throughout the intestinal wall. Peyer’s patches consist of highly organized ovoid-shaped follicles, classified as non-encapsulated lymphatic tissues, populated with B cells, T cells, macrophages, and dendritic cells and function as an organism’s intestinal surveillance. Limited work compares the gene profiles of Peyer’s patches derived from different intestinal regions. In the current study, we first performed whole transcriptome analysis using RNAseq to compare duodenal and ileal Peyer’s patches obtained from the small intestine of Long Evans rats. Of the 12,300 genes that were highly expressed, 18.5% were significantly different between the duodenum and ileum. Using samples obtained from additional subjects ( n = 10), we validated the novel gene expression patterns in Peyer’s patches obtained from the three regions of the small intestine. Rats had a significantly reduced number of Peyer’s patches in the duodenum in comparison to either the jejunum or ileum. Regional differences in structural, metabolic, and immune-related genes were validated. Genes such as alcohol dehydrogenase 1, gap junction protein beta 2, and serine peptidase inhibitor clade b, member 1a were significantly reduced in the ileum in comparison to other regions. On the other hand, genes such as complement C3d receptor type, lymphocyte cytosolic protein 1, and lysozyme C2 precursor were significantly lower in the duodenum. In summary, the gene expression pattern of Peyer’s patches is influenced by intestinal location and may contribute to its role in that segment.

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Expression profiling of purified male germ cells: stage-specific expression patterns related to meiosis and postmeiotic development

Physiological Genomics ◽

10.1152/physiolgenomics.00215.2004 ◽

2006 ◽

Vol 24 (2) ◽

pp. 75-85 ◽

Cited By ~ 36

Author(s):

Alan L. Y. Pang ◽

Warren Johnson ◽

Neelakanta Ravindranath ◽

Martin Dym ◽

Owen M. Rennert ◽

...

Keyword(s):

Gene Expression ◽

Germ Cells ◽

Expression Profiling ◽

Intracellular Transport ◽

Expression Patterns ◽

Male Gamete ◽

Specific Expression ◽

Differential Expression Pattern ◽

Pachytene Spermatocytes ◽

Cycle Regulation

Gene expression profiling was performed using the National Institute on Aging 15,000-cDNA microarray to reveal the differential expression pattern of 160 genes between meiotic pachytene spermatocytes and postmeiotic round spermatids of the mouse. Our results indicate that more genes are expressed in spermatids than in spermatocytes. Genes participating in cell cycle regulation and chromatin structure and dynamics are preferentially expressed in spermatocytes, while genes for protein turnover, signal transduction, energy metabolism, and intracellular transport are prevalent in spermatids. This suggests that a switch of functional requirement occurs when meiotic germ cells differentiate into haploid spermatids. Concordant expression patterns were obtained when quantitative real-time polymerase chain reaction was performed to verify the microarray data. Interestingly, the majority of the differentially expressed genes were underrepresented in mitotic type A spermatogonia, and they were preferentially expressed in the testis. Our results suggest that an even higher proportion of the mouse genome is devoted to male gamete development from meiosis than was previously estimated. We also provide evidence that underscores the advantage of using purified germ cells over whole testes in profiling spermatogenic gene expression to identify transcripts that demonstrate stage-specific expression patterns.

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Genome-wide expression profiling; a panel of mouse tissues discloses novel biological functions of liver X receptors in adrenals

Journal of Molecular Endocrinology ◽

10.1677/jme.1.01508 ◽

2004 ◽

Vol 33 (3) ◽

pp. 609-622 ◽

Cited By ~ 39

Author(s):

Knut R Steffensen ◽

Soek Ying Neo ◽

Thomas M Stulnig ◽

Vinsensius B Vega ◽

Safia S Rahman ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiling ◽

Target Genes ◽

Uncoupling Protein ◽

Expression Profiles ◽

Expression Patterns ◽

Global Gene Expression ◽

Liver X Receptors ◽

Mouse Tissues ◽

X Receptors

The liver X receptors α and β (LXRα and LXRβ ) are members of the nuclear receptor superfamily of proteins which are highly expressed in metabolically active tissues. They regulate gene expression of critical genes involved in cholesterol catabolism and transport, lipid and triglyceride biosynthesis and carbohydrate metabolism in response to distinct oxysterols and intermediates in the cholesterol metabolic pathway. The biological roles of the LXRs in tissues other than liver, intestine and adipose tissue are poorly elucidated. In this study we used global gene-expression profiling analysis to detect differences in expression patterns in several tissues from mice fed an LXR agonist or vehicle. Our results show that LXR plays an important role in the kidney, lung, adrenals, brain, testis and heart where several putative LXR target genes were found. The effects of the LXRs were further analysed in adrenals where treatment with an LXR agonist induced expression of adrenocorticotrophic hormone receptor, suppressed expression of uncoupling protein (UCP)-1 and UCP-3 as well as several glycolytic enzymes and led to increased serum corticosterone levels. These results indicate novel biological roles of the LXR including regulation of energy metabolism, glycolysis and steroidogenesis in the adrenals via alteration of expression profiles of putative target genes.

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Clinical phenotype and gene expression profile in Crohn's disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00321.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. G298-G304 ◽

Cited By ~ 13

Author(s):

Claudio Csillag ◽

Ole Haagen Nielsen ◽

Rehannah Borup ◽

Finn Cilius Nielsen ◽

Jørgen Olsen

Keyword(s):

Gene Expression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intracellular Transport ◽

Clinical Phenotype ◽

Expression Profiles ◽

Expression Patterns ◽

Principal Component ◽

Gene Profiling ◽

Gene Expression Patterns

The clinical course varies significantly among patients with Crohn's disease (CD). This study investigated whether gene expression profiles generated by DNA microarray technology might predict disease progression. Biopsies from the descending colon were obtained colonoscopically from 40 CD patients. Gene profiling analyses were performed using a Human Genome U133 Plus 2.0 GeneChip Array, and summarization into a single expression measure for each probe set was performed using the robust multiple array procedure. Principal component analysis demonstrated that three components explain two-thirds of the total variation. The most important parameters for the determination of the colonic gene expression patterns were the presence of disease (CD) and presence of inflammation. Superimposition of clinical phenotype data revealed a grouping of the samples from patients with stenosis toward negative values on the axis of the second principal component. The functional annotation analysis suggested that the expression of genes involved in intracellular transport and cytoskeletal organization might influence the development of stenosis. In conclusion, even though most variation in the colonic gene expression patterns is due to presence or absence of CD and inflammation status, the development of stenosis is a parameter that affects colonic gene expression to some extent.

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Array analysis of gene expression in connexin-43 null astrocytes

Physiological Genomics ◽

10.1152/physiolgenomics.00062.2003 ◽

2003 ◽

Vol 15 (3) ◽

pp. 177-190 ◽

Cited By ~ 67

Author(s):

Dumitru A. Iacobas ◽

Marcia Urban-Maldonado ◽

Sanda Iacobas ◽

Eliana Scemes ◽

David C. Spray

Keyword(s):

Gene Expression ◽

Gap Junction ◽

Dna Sequences ◽

Connexin 43 ◽

Expression Patterns ◽

Dna Arrays ◽

Cultured Astrocytes ◽

Junction Protein ◽

High Degree ◽

The Impact

Connexin-43 (Cx43) is the most abundant gap junction protein in brain, where it is found primarily between astrocytes. Although the morphology of astrocytes from Cx43-null (knockout, KO) mice is similar to that of wild-type (WT) astrocytes, KO astrocytes exhibit reduced growth rate in culture. To evaluate the impact of deletion of Cx43 on other genes, including those encoding cell cycle proteins, we used DNA arrays to determine expression patterns in cultured astrocytes from sibling Cx43-null and WT mice. RNA samples extracted from astrocytes cultured from WT and Cx43-null neonatal mice were dye labeled and individually cohybridized with a reference of labeled cDNAs pooled from a variety of tissues on 8 gene arrays containing 8,975 mouse DNA sequences. Normal variability in expression of each gene was evaluated and incorporated into “expression scores” to statistically compare expression levels between WT and KO samples. In Cx43-null astrocytes, 4.1% of the 4,998 adequately quantifiable spots were found to have significantly ( P < 0.05) decreased hybridization compared with controls, and 9.4% of the spots showed significantly higher hybridization. The significantly different spots corresponded to RNAs encoding 252 known proteins, many not previously linked to gap junctions, including transcription factors, channels and transporters, cell growth and death signals, enzymes and cell adhesion molecules. These data indicate a surprisingly high degree of impact of deletion of Cx43 on other astrocyte genes, implying that gap junction gene expression alters numerous processes in addition to intercellular communication.

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Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm

Development ◽

10.1242/dev.119.3.567 ◽

1993 ◽

Vol 119 (3) ◽

pp. 567-578 ◽

Cited By ~ 55

Author(s):

A.P. Monaghan ◽

K.H. Kaestner ◽

E. Grau ◽

G. Schutz

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Expression Patterns ◽

Primitive Streak ◽

Definitive Endoderm ◽

Specific Gene ◽

Axis Formation ◽

Specific Gene Expression ◽

Mouse Tissues ◽

Alpha Beta

The HNF-3 alpha, beta and gamma genes constitute a family of transcription factors that are required for hepatocyte-specific gene expression of a number of genes, e.g. transthyretin, alpha-1 antitrypsin and tyrosine aminotransferase. These genes share a highly conserved DNA-binding domain first found in the Drosophila gene, forkhead, which is required for the normal patterning of the developing gut and central nervous system in Drosophila. In adult mouse tissues, transcripts from HNF-3 alpha and beta have been localised to the liver, intestine and lung, whereas HNF-3 gamma is found in the liver, intestine and testis. In light of the early developmental significance of forkhead in Drosophila, we have compared the patterns of expression of HNF-3 alpha, beta and gamma mRNAs during murine embryogenesis. We find that these genes are sequentially activated during development in the definitive endoderm. HNF-3 beta mRNA is expressed in the node at the anterior end of the primitive streak in all three germ layers and is the first gene of this family to be activated. Subsequently, HNF-3 alpha is transcribed in the primitive endoderm in the region of the invaginating foregut and HNF-3 gamma appears upon hindgut differentiation. These genes have different anterior boundaries of mRNA expression in the developing endoderm and transcripts are found in all endoderm-derived structures that differentiate posterior to this boundary. Therefore, we propose that these genes define regionalization within the definitive endoderm. Furthermore, differential mRNA expression of HNF-3 alpha and beta is detected in cells of the ventral neural epithelium, chordamesoderm and notochord. In the neural epithelium, expression of HNF-3 alpha and beta mRNA becomes localised to cells of the floor plate. We propose that, in addition to their characterised requirement for liver-specific gene expression, HNF-3 alpha and beta are required for mesoderm and neural axis formation. We also conclude that HNF-3 beta is the true orthologue of the Drosophila forkhead gene.

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Distinct gene expression profiles in adult mouse heart following targeted MAP kinase activation

Physiological Genomics ◽

10.1152/physiolgenomics.00224.2005 ◽

2006 ◽

Vol 25 (1) ◽

pp. 50-59 ◽

Cited By ~ 31

Author(s):

Scherise Mitchell ◽

Asuka Ota ◽

William Foster ◽

Bin Zhang ◽

Zixing Fang ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Map Kinase ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Mouse Heart ◽

Matrix Remodeling ◽

Long Term Effects ◽

Kinase Activation

Three major MAP kinase signaling cascades, ERK, p38, and JNK, play significant roles in the development of cardiac hypertrophy and heart failure in response to external stress and neural/hormonal stimuli. To study the specific function of each MAP kinase branch in adult heart, we have generated three transgenic mouse models with cardiac-specific and temporally regulated expression of activated mutants of Ras, MAP kinase kinase (MKK)3, and MKK7, which are selective upstream activators for ERK, p38, and JNK, respectively. Gene expression profiles in transgenic adult hearts were determined using cDNA microarrays at both early (4–7 days) and late (2–4 wk) time points following transgene induction. From this study, we revealed common changes in gene expression among the three models, particularly involving extracellular matrix remodeling. However, distinct expression patterns characteristic for each pathway were also identified in cell signaling, growth, and physiology. In addition, genes with dynamic expression differences between early vs. late stages illustrated primary vs. secondary changes on MAP kinase activation in adult hearts. These results provide an overview to both short-term and long-term effects of MAP kinase activation in heart and support some common as well as unique roles for each MAP kinase cascade in the development of heart failure.

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