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At least 19 recordsLinked to original sources
PubMed2002

Antisense RNAs in bacteria and their genetic elements.

Antisense RNA-mediated regulation is widespread in bacteria. Most antisense RNA control systems have been found in plasmids, phages, and transposons. Fewer examples were identified in bacterial chromosomes. This chapter summarizes our current knowledge about antisense RNAs with respect to their occurrence, their biological roles, and their diverse mechanisms of action. Examples of cis- or trans-encoded antisense RNAs are discussed, and their properties compared. Most antisense RNAs are posttranscriptionally acting inhibitors of target genes, but a few examples of activator antisense RNAs are known. The implications of RNA structure on topologically and kinetically favored binding pathways are addressed, and solutions that have evolved to permit productive interactions between intricately folded RNAs are discussed. Finally, we describe how particular properties of individual antisense/target RNA systems match their respective biological roles.

Bacteria↗
PubMed1998

Antisense peptides: a critical mini-review.

Antisense peptides are defined as those generated from the non-coding strand of DNA, and represent a peptide analog to antisense RNA technologies. Peptides generated from both parallel and anti-parallel readings of the non-coding strand of DNA have displayed biological activity, although considerable controversy exists concerning the mechanism(s) by which these "anti-peptides" exert their effects. This paper provides a critical review of some of the key data and issues defining this emerging field and focuses on contradictions and discrepancies in the current studies. We also suggest some directions for future research such as more physico-chemical studies and the use of combinatorial chemistry techniques combined with solid phase binding studies to test, once and for all, the generality and specificity of antisense peptide interactions.

Amino Acids↗
PubMed1996

Antisense and ribozyme constructs in transgenic animals.

Geneticists have long sought the ability to add or subtract individual genes from an organism's genome, or to be able to alter the level of expression of a gene in a targeted, developmentally and tissue-specific manner. The development of transgenic technology realized the possibilities of increasing the expression of a specific gene or the transfer of a new gene into an animal. Homologous recombination techniques allow the deletion or alteration of a gene in vivo. The production of transgenic animals incorporating a gene construct that expresses a complimentary antisense RNA to a targeted gene, or an antisense RNA incorporating a catalytic, ribozyme sequence, have been suggested as a potential mechanism for obtaining the developmentally and tissue-specific down-regulation of expression of a targeted gene in vivo. In this paper we review the current literature with respect to the application of antisense and ribozyme constructs in transgenic animals and conclude that such constructs can effectively downregulate the level of mRNA from a target gene, the amount of protein produced in the cell, and result in phenotypic consequences.

Animals↗
PubMed1996

Expression of cytochrome P45011B1 mRNA in the brain of normal and hypertensive transgenic rats.

Cytochrome P45011B1 (11 beta-hydroxylase) was detected in the brain of male rats by in situ hybridization methods. Normal Sprague-Dawley rats were compared to the transgenic strain TGR(mRen2)27, characterized by the expression of the murine Ren-2d renin gene and the development of severe hypertension. Specific riboprobes were generated by in the vitro transcription of a 152 base-pair long cDNA template 35S-labeled riboprobes were hybridized to cryostat sections from adrenal glands and from two different levels of the brain using standard protocols and varying washing conditions. After exposure of the radiolabeled sections to X-ray film, the signals were quantified and compared. Following autoradiography and counterstaining, cytochrome P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis of the adrenal cortex and in distinct layers of the cerebral cortex. High signal densities were obtained in the layers II-IV of the neocortex and in the layer II of the piriform cortex, although the concentrations of cytochrome P45011B1 mRNA were remarkably lower in the central nervous system as compared to adrenal glands. As revealed by the semi-quantitative analysis, there was a slight increase in adrenal 11 beta-hydroxylase mRNA in the transgenic rats, whereas the brain seems to express nearly the same amount of this enzyme in both strains. The cytochrome P45011B1 mRNA expression in distinct cells, probably nerve cells, and especially in regions with high densities of glucocorticoid receptors points to a possible function of brain derived corticosterone in receptor activation.

Adrenal Glands↗
PubMedDate not supplied

Zebrafish as a neurotoxicological model.

At a time when common regulatory pathways are being identified in several different species and genomics is beginning to allow comparisons of genes, how they are arranged on chromosomes and how they are regulated, zebrafish has emerged as a valuable and complementary vertebrate model. Some of the characteristics that prove of value are described and illustrated. Fluorescent transgenic lines of zebrafish embryos are presented for time-line studies with neurotoxicants. While genetic knockout technology has yet to be developed for the model, the anti-sense, morpholino approach allows for knockdown of expression of genes for the 3 day, embryonic period. This can provide for phenocopies of mutant genes for those genes essential to embryonic development or it can provide for a limited inhibition of gene expression that allows subsequent development of the fish. With the zebrafish genomic sequencing effort, microarray technology is now developing for the model system. These resources and technologies allow one to challenge the system with toxicants, and to view the immediate effects of the toxicants with transgenic embryos that fluoresce in part or all of the nervous system. Behavioral and learning protocols have been developed for the organism so that early exposures can be assayed for effects upon adult fish. Microarray technology should allow for one to identify specific genes and pathways affected by a neurotoxicant. In the future, these approaches should provide a working protocol for exploring molecular mechanisms of neurotoxicants. This type of complementary approach should then allow for more efficient examination and testing of mechanisms in mammalian models.

Animals↗
PubMed2002

Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model.

The longer life span in dwarf mice suggests that a reduction in the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis retards aging and extends the life span in mammals. We tested this hypothesis in a transgenic strain of rats whose GH gene was suppressed by an anti-sense GH transgene. Male rats homozygous for the transgene (tg/tg) had a reduced number of pituitary GH cells, a lower plasma concentration of IGF-1, and a dwarf phenotype. Heterozygous rats (tg/-) had an intermediate phenotype in plasma IGF-1, food intake, and body weight between tg/tg and control (-/-) rats. The life span of tg/tg rats was 5 to 10% shorter than -/- rats. In contrast, the life span of tg/- rats was 7 to 10% longer than -/- rats. Pathological analysis suggested that neoplasms caused earlier death in tg/tg rats; in contrast, tg/- rats had reduced nonneoplastic diseases and a prolonged life span. Immunological analysis revealed a smaller population and lower activity of splenic natural killer cells in tg/tg rats. The results of the present study support the hypothesis, but suggest that there is an optimal level of the GH-IGF-1 axis to maximize survival in mammals.

Animals↗
PubMed1999

A novel 111In-labeled antisense DNA probe with multi-chelating sites (MCS-probe) showing high specific radioactivity and labeling efficiency.

A multi-aminolinked oligodeoxynucleotide (ODN) was synthesized by substitution of dT with aminolinked dU in the sequence, following conjugation with isothiocyanobenzyl-EDTA (IBE) for 111In labeling. As a model target gene, the c-erbB-2 protooncogene was used. The probability of the number of aminolinked dU in the 20mer ODN was 5, but there were actually 3 and 4 in the selected antisense and sense ODNs, respectively. The IBE/ODN conjugation levels of probes with multi-chelating sites (MCS-probe) were 1.6 (antisense) and 2.4 (sense), more than 50 times higher than those of our previous studies using 5'-end aminolinked ODNs (IBE/ODN = 0.03). Labeling studies using the MCS-probe and 111In indicated that specific radioactivity as high as 48 MBq/nmol could be obtained with a labeling efficiency of over 90%. The 111In-antisense-MCS-probe could bound to sense ODN under physiological conditions, but the 111In-sense-MCA-probe could not. Thus, side-chain modification of ODN for metal labeling is considered to be useful for antisense techniques.

Antisense Elements (Genetics)↗
PubMed1991

Informational drugs: a new concept in pharmacology.

Drugs that contain information encoded in them are intended to interfere with great specificity in the transfer of information within the cell, thus providing selective therapeutic advantage. It is proposed that such drugs can be classified as informational drugs.

Antisense Elements (Genetics)↗
PubMed2001

Zebrafish myelopoiesis and blood cell development.

The zebrafish (Danio rerio) animal model offers a unique opportunity to discover novel genes required for the control of normal vertebrate myeloid cell development. It is well suited for both developmental and genetic analyses: eg, genome-wide chemical mutagenesis screens have led to the identification of specific new genes affecting vertebrate erythropoiesis. Mutants defective in one or more hematopoietic functions will be useful as models of human disease and will assist in the elucidation of lineage-specific developmental programs. By using a combination of forward genetic mutagenesis screens and emerging strategies based on transgenic and antisense knockdown approaches, it should be possible to dissect the genetic programs that lead to myeloproliferative/myelodysplastic syndromes and to acute myeloid leukemia.

Animals↗
PubMed2005

Anatomical and functional characterization of clock gene expression in neuroendocrine dopaminergic neurons.

Oscillations of gene expression and physiological activity in suprachiasmatic nucleus (SCN) neurons result from autoregulatory feedback loops of circadian clock gene transcription factors. In the present experiment, we have determined the pattern of PERIOD1 (PER1), PERIOD2 (PER2), and CLOCK expression within neuroendocrine dopaminergic (DAergic) neurons (NDNs) of ovariectomized (OVX) rats. We have also determined the effects of per1, per2, and clock mRNA knockdown in the SCN with antisense deoxyoligonucleotides (AS-ODN) on DA release from NDNs. Diurnal rhythms of PER1 and PER2 expression in tuberoinfundibular DAergic (TIDA) and periventricular hypophyseal DAergic (PHDA) neurons, peaked at circadian time (CT)18 and CT12, respectively. Rhythms of PER1 expression in tuberhypophyseal neuroendocrine DAergic (THDA) neurons were undetectable. Rhythms of PER2 expression were found in all three populations of NDNs, with greater levels of PER2 expression between CT6 and CT12. AS-ODN injections differentially affected DA turnover in the axon terminals of the median eminence (ME), neural lobe (NL) and intermediate lobe (IL) of the pituitary gland, resulting in a significant decrease in DA release in the early subjective night in the ME (TIDA), a significant increase in DA release at the beginning of the day in the IL (PHDA), and no effect in the NL (THDA). AS-ODN-treatment induced a rhythm of DA concentration in the anterior lobe, with greater DA levels in the middle of the day. These data suggest that clock gene expression, particularly PER1 and PER2, within NDNs may act to modulate diurnal rhythms of DA release from NDNs in the OVX rat.

ARNTL Transcription Factors↗
PubMed2006

Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome.

BACKGROUND: Understanding the functional role(s) of the more than 20,000 proteins of the vertebrate genome is a major next step in the post-genome era. The approximately 4,000 co-translationally translocated (CTT) proteins - representing the vertebrate secretome - are important for such vertebrate-critical processes as organogenesis. However, the role(s) for most of these genes is currently unknown. RESULTS: We identified 585 putative full-length zebrafish CTT proteins using cross-species genomic and EST-based comparative sequence analyses. We further investigated 150 of these genes (Figure 1) for unique function using morpholino-based analysis in zebrafish embryos. 12% of the CTT protein-deficient embryos resulted in specific developmental defects, a notably higher rate of gene function annotation than the 2%-3% estimate from random gene mutagenesis studies. CONCLUSION: This initial collection includes novel genes required for the development of vascular, hematopoietic, pigmentation, and craniofacial tissues, as well as lipid metabolism, and organogenesis. This study provides a framework utilizing zebrafish for the systematic assignment of biological function in a vertebrate genome.

Amino Acid Sequence↗
PubMed1992

[Anti-sense peptide].

Explore the source record for details and available documents.

Antisense Elements (Genetics)↗
PubMed1993

Antisense technology: biological utility and practical considerations.

Antisense RNA and DNA techniques have been developed as a relatively recent approach to the specific modulation of gene expression in vitro and in vivo. This review discusses general considerations for the application of antisense techniques. We shall examine the relative advantages and disadvantages of DNA versus RNA techniques, as well as the common pitfalls peculiar to each strategy.

Animals↗
PubMed1992

Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes.

The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure. We report here the development of transgenic rats carrying the human angiotensinogen TGR-(hAOGEN) and human renin TGR(hREN) genes. The plasma levels and tissue distribution of the transcription and translation products from both genes are described. A unique species specificity of the enzyme kinetics was observed. The human RAS components in the transgenic rats did not interact with the endogenous rat RAS in vivo. Instead, infusions of exogenous human RAS components specifically interacted with human transgene translation products. Thus, infusion of human renin in TGR(hAOGEN) led to an increase of angiotensin II and an elevation of blood pressure, which could not be antagonized by the human-specific renin enzyme inhibitor Ro 42-5892. Rat renin also elevated blood pressure and angiotensin II in TGR(hAOGEN); however, this effect was not antagonized by the human renin inhibitor. Compared to mice, rats offer the advantage of chronic instrumentation and repetitive, sophisticated, hemodynamic, and endocrinological investigations. Thus, transgenic rat models with human-specific enzyme kinetics permit primate-specific analyses in non-primate in vivo and in vitro experimental systems.

Angiotensin II↗