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PubMed2006

Characterization of cannabinoid-binding sites in zebrafish brain.

We present here the pharmacological characterization of cannabinoid-binding sites in zebrafish brain homogenates using radiolabeled binding techniques. The nonselective agonist [3H]-CP55940 binds with high affinity (KD = 0.50+/-0.06 nM and a Bmax = 1047+/-36.01 fmol/mg protein), displaying one binding site. The slightly CB2 selective agonist [3H]-WIN55212-2 also binds with high affinity to zebrafish brain membranes displaying two different binding sites with affinities KD1 = 0.35+/-0.09 nM and KD2 = 105.81+/-66.36 nM. Competition binding assays using [3H]-WIN55212-2 and several unlabeled ligands were performed. WIN55212-2 significantly displaced the tritiated ligand binding showing the two binding sites observed with its tritiated homologous, while the slightly selective CB1 cannabinoid ligand HU-210, the nonselective cannabinoid ligand CP55940 and the endogenous cannabinoid ligand anandamide presented one binding site. Also, the functionality of these cannabinoid sites was analyzed using the known [35S]GTPgammaS assay. All the agonist used presented an agonist profile and the rank order for potency was HU-210 > WIN55212-2 > CP55940 >anandamide. Our results provide evidence that, although some of the typical cannabinoid ligands for mammalian receptors do not fully recognize the cannabinoid-binding sites in zebrafish brain, the activity of the endogenous zebrafish cannabinoid system might not significantly differ from that displayed by the cannabinoid system described in other species. Hence the study of zebrafish cannabinoid activity may contribute to an understanding of the endogenous cannabinoid system in higher vertebrates.

Animals↗

PubMed2006

Antipsychotics produce locomotor impairment in larval zebrafish.

Zebrafish has been a favored vertebrate genetic model organism for studying developmental processes. It also holds a great potential for understanding the genetic basis of behavior and associated behavioral disorders. Despite such potential, their use in the study of behavior is greatly under-explored. It is well known that multiple classes of drugs used to treat psychiatric diseases produce extrapyramidal side (EPS) effects and consequent movement disorders in humans. The underlying molecular causes of these drug-induced movement disorders are poorly understood. Here we report that zebrafish treated with the antipsychotics fluphenazine and haloperidol (both of which can induce severe EPS in humans) develop movement defects. In contrast, another antipsychotic olanzapine, which produces mild to little EPS in humans, leads to minimal movement defects in zebrafish. These results establish a rapid assay system in which the effects of EPS-inducing agents can be assessed. Thus, future genetic screening in zebrafish shall identify genes and pathways that elucidate drug-induced movement disorder in human as well as provide insights into the brain control of locomotor activity. Future chemical screening in zebrafish may act as a preclinical test for the EPS effect of certain drugs, as well as a test used to researching drugs made to counteract the effects of EPS.

Animals↗

PubMed2004

Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening.

Larval zebrafish are used extensively for developmental genetic studies due to their salient features, such as small size, external development, optical transparency, and accessibility in large numbers. However, their use for the study of drug and alcohol abuse has not been explored. Here we investigated the response of larval zebrafish to acute treatment of alcohol. Our analyses showed that like adults, the larval zebrafish exhibited a dose-dependent locomotor response to ethanol: intermediate doses led to hyperactivity, whereas high doses have a neurodepressive effect resulting in hypoactivity and sedation. Alcohol also induced morphological changes of melanocytes, providing a visible cellular measure of the biological effects of alcohol in vivo. In addition, alcohol induced thigmotaxis behavior (preference for the edge of a compartment). In the behaviors we analyzed, genetic background influenced the locomotor responses to alcohol. The present study demonstrates that larval zebrafish exert a response to the acute treatment of alcohol, which is genetically modifiable. Therefore, the larval zebrafish represent a tractable vertebrate model system for a large-scale genetic analysis of the biological effects of alcohol.

Animals↗

PubMed2006

Anxiolytic effects of nicotine in zebrafish.

Anxiolytic effects of nicotine have been documented in studies with rodents and humans. Understanding the neural basis of nicotine-induced anxiolysis can help both with developing better aids for smoking cessation as well as with the potential development of novel nicotinic ligands for treating anxiety. Complementary non-mammalian models may be useful for determining the molecular bases of nicotine effects on neurobehavioral function. The current project examined whether a zebrafish model of anxiety would be sensitive to nicotine. When zebrafish are placed in a novel environment, they dive to the bottom of the tank. In the wild, diving could help to escape predation. We tested the anxiolytic effect of nicotine on the novelty-elicited diving response and subsequent habituation. Zebrafish placed in a novel tank spent the majority of time at the bottom third of the tank during the first minute of a 5-min session and then show a gradual decrease in time spent at the tank bottom. Nicotine treatment at 100 mg/l for 3 min by immersion before testing caused a significant decrease in diving throughout the session, while 50 mg/l was effective during the first minute when the greatest bottom dwelling was seen in controls. Nicotine effects were reversed by the nicotinic antagonist mecamylamine given together with nicotine, but not when administered shortly before the test session after prior nicotine dosing. This implies that the effect of nicotine on diving was due to net stimulation at nicotinic receptors, an effect that is blocked by mecamylamine; and that once invoked, this effect is no longer dependent on continuing activation of nicotinic receptors. The effect of nicotine on diving did not seem to be the result of a general disorientation of the fish. The 100 mg/ml nicotine dose was shown in our earlier study to significantly improve spatial-discrimination learning in zebrafish. Nicotine-induced anxiolytic effects can be modeled in the zebrafish. This preparation will help in the investigation of the molecular bases of this effect.

Animals↗

PubMed2006

Zebrafish (Danio rerio) as a model for the study of vaccination against viral haemorrhagic septicemia virus (VHSV).

The rhabdovirus viral haemorrhagic septicemia virus (VHSV) is the etiological agent of one of the most important salmonid viral diseases. In the present work, the ability of VHSV to infect and replicate in zebrafish at low temperature (15 degrees C) was demonstrated. Zebrafish was also used to determine the effectiveness of the recombinant virus rIHNV-Gvhsv GFP as a live attenuated vaccine against the virulent VHSV strain. Fish intraperitoneally injected with 3 x 10(6) to 3 x 10(5)TCID50/ml of the wild type VHSV showed a 100% of cumulative mortality, meanwhile only 57% of mortality was obtained in bath infections. Infected fish showed external clinical signs and histological observations revealed the appearance of small haemorrhages in the muscle, kidney, liver and dermis. Neither mortalities nor clinical signs were recorded in fish infected with a live attenuated recombinant virus. By RT-PCR technique, VHSV was detected in all the organs as early as 24h, but the recombinant virus was not detected in all the sampled days. VHSV was able to replicate "in vitro" in head kidney cells but the replication capacity of the attenuated viral strain was limited. The recombinant virus rIHNV-Gvhsv GFP was able to protect against VHSV with a survival rate ranging from 20% to 60% depending of the vaccine dose. The increase of TLR3, IFNalphabeta, Mx, IFNgamma and TNFalpha expression at 72h post-infection in the kidney of VHSV-infected fish contrasted with the results obtained with the avirulent virus, which did not induce an increment of this expression in infected fish. Zebrafish is a suitable animal model to study VHSV infection and immune (innate and adaptive) responses and, more importantly, we demonstrate for the first time the usefulness of the zebrafish as a vaccination model to viral diseases. In addition, the high protection obtained with the live attenuated virus demonstrates that the zebrafish is able to mount an efficient antiviral immune response at 15 degrees C.

Animals↗

PubMed2006

Behavioral spectral sensitivity of the zebrafish (Danio rerio).

While the zebrafish (Danio rerio) continues to become an important animal model for the investigation of the genetic and physiological bases of visual processing of the vertebrate retina, its visual behavior, particularly regarding color processing, has received little attention. The purpose of this study was to obtain behavioral spectral sensitivity functions from adult zebrafish using an appetitive instrumental conditioning procedure. A three-chamber maze was implemented to train light-adapted adult zebrafish to swim into the chamber that contained a suprathreshold monochromatic stimulus for a food reward. Visual threshold was determined by varying the stimulus irradiance using a 'two-down one-up' staircase procedure. Threshold values were obtained for wavelengths from 340 to 640 nm. Spectral sensitivity functions obtained show contributions from two nonopponent cone mechanisms (UV and S) and two opponent mechanisms (M-S and L-M). These cone mechanisms are qualitatively similar to those obtained via physiological measures from the On-responses of the zebrafish retina and optic tectum. However, the functions are not quantitatively similar suggesting that further visual processing takes place beyond the processing of the retinal circuitry and processing of the initial stages of the optic tectum. These results demonstrate that the zebrafish is an excellent model to examine and compare the relationship between physiological and behavioral color processing.

Animals↗

PubMed2006

A beta1,4-galactosyltransferase is required for convergent extension movements in zebrafish.

Our understanding of how complex carbohydrates function during embryonic development is still very limited, primarily due to the large number of glycosyltransferases now known to be involved in their synthesis. To overcome these limitations, we have taken advantage of the zebrafish system to analyze the function of complex carbohydrates during development by down-regulating the expression of specific glycosyltransferases. Herein, we report the identification of the zebrafish ortholog of mammalian beta1,4-galactosyltransferase I, beta4GalT1, and its requirement for proper convergent extension movements during gastrulation. beta4GalT1 is expressed in the oocyte and throughout the embryo during the first 24 h of development. Knockdown of zebrafish beta4GalT1 by two independent morpholino oligonucleotides results in embryos with a truncated anterior-posterior axis, as well as elongated somites and moderate defects in the patterning of the head mesenchyme. Co-injection of zebrafish beta4GalT1 mRNA returns galactosyltransferase activity to control levels and rescues the defects produced by morpholino oligonucleotides. In situ hybridizations of various molecular markers reveal that the axial mesoderm of epiboly stage embryos is abnormally widened in beta4GalT1 morphants, indicative of abnormal convergent extension. Consistent with this, the rate of anterior-posterior axis elongation is reduced relative to control-injected embryos, similar to that seen in known convergent extension mutants. Among the many potential substrates for beta4GalT1 is laminin, a principle component of the extracellular matrix that supports cell movements such as those that occur during convergent extension. Previous in vitro studies have shown that the galactosylation status of laminin directly influences its ability to support cell spreading and migration. In this regard, laminin isolated from beta4GalT1 morphant embryos is poorly galactosylated, which may contribute to defective cell migration during convergent extension movements. This work demonstrates that zebrafish can be used to identify critical developmental roles for specific glycosyltransferases that would not be obvious otherwise, such as an absolute requirement for beta4GalT1 during convergent extension movements.

Amino Acid Sequence↗

PubMed2004

Cloning of zebrafish ovarian P450c17 (CYP17, 17alpha-hydroxylase/17, 20-lyase) and characterization of its expression in gonadal and extra-gonadal tissues.

Cytochrome P450c17 (CYP17, 17alpha-hydroxylase/17, 20-lyase) has been viewed as a critical enzyme for the biosynthesis of gonadal and adrenal steroids in vertebrates. A full-length cDNA coding for P450c17 has been cloned from the zebrafish ovary. It encodes 519 amino acids and shares high sequence identity with that of fathead minnow (92%), rainbow trout (74%), chicken (64%), rat (47%), and human (48%). Northern blot analysis demonstrated that it is predominantly expressed in the ovary and testis; however, a weak hybridization signal was also detected in the whole kidney of the zebrafish, suggesting a role for P450c17 in the steroidogenesis of both gonads and renal/interrenal tissues. We further examined the expression of P450c17 in the developing ovarian follicles. Northern analysis and RT-PCR revealed abundant expression of the enzyme in the follicles of all major stages including pre-vitellogenic, vitellogenic and post-vitellogenic full-grown follicles; however, unlike P450c17 in the rainbow trout and eel, the expression of zebrafish P450c17 did not show significant temporal difference among different developmental stages, similar to the finding in the fathead minnow. The constitutive nature of P450c17 expression during zebrafish follicle development may partly explain the poor transcriptional response of the enzyme to the treatments with gonadotropin or activin, both of which enhance oocyte maturation in this species. It is also of interest to note that when assayed by RT-PCR, the enzyme P450c17 also seemed to be expressed in several other non-gonadal tissues including the brain, gill, liver and intestine, and its expression did not show significant sexual dimorphism in the brain of adult zebrafish. The physiological relevance of these findings remains to be further elucidated.

Amino Acid Sequence↗

PubMed2003

Cardiac neural crest contributes to cardiomyogenesis in zebrafish.

In birds and mammals, cardiac neural crest is essential for heart development and contributes to conotruncal cushion formation and outflow tract septation. The zebrafish prototypical heart lacks outflow tract septation, raising the question of whether cardiac neural crest exists in zebrafish. Here, results from three distinct lineage-labeling approaches identify zebrafish cardiac neural crest cells and indicate that these cells have the ability to generate MF20-positive muscle cells in the myocardium of the major chambers during development. Fate-mapping demonstrates that cardiac neural crest cells originate both from neural tube regions analogous to those found in birds, as well as from a novel region rostral to the otic vesicle. In contrast to other vertebrates, cardiac neural crest invades the myocardium in all segments of the heart, including outflow tract, atrium, atrioventricular junction, and ventricle in zebrafish. Three distinct groups of premigratory neural crest along the rostrocaudal axis have different propensities to contribute to different segments in the heart and are correspondingly marked by unique combinations of gene expression patterns. Zebrafish will serve as a model for understanding interactions between cardiac neural crest and cardiovascular development.

Animals↗

PubMed2002

Identification and structural analysis of a zebrafish apo and holo cellular retinol-binding protein.

Cellular retinol-binding proteins (CRBPs) are cytoplasmic retinol-specific binding proteins. Mammalian CRBPs have been thoroughly characterised previously. Here we report on the identification and X-ray structural analysis of the apo (1.7A resolution) and holo (1.4A resolution) forms of a zebrafish CRBP. According to amino acid sequence and structure analyses, the zebrafish CRBP that we have identified resembles closely mammalian CRBP II, suggesting that it is the zebrafish orthologue of this mammalian CRBP type. Zebrafish CRBP forms a tight complex with all-trans retinol, producing an absorption spectrum similar to those of mammalian holo-CRBPs, albeit slightly blue-shifted. The superposition of the alpha-carbon atoms of the liganded (complexed with retinol) and unliganded forms of zebrafish CRBP shows significant differences in correspondence of the betaC-betaD (residues 55-58) and betaE-betaF (residues 74-77) turns, providing evidence for the occurrence of conformational changes accompanying retinol binding/release. Remarkable and well-defined ligand-dependent conformational changes in the protein region comprising the two beta-turns affect both the main chain and the side-chains of several residues. The two beta-turns project towards the interior of the cavity devoid of ligand of the apoprotein. The side-chains of F57, Y60 and L77 change substantially their orientation and position in the apoprotein relative to the holoprotein. In the beta-barrel internal cavity of apo-CRBP they occupy some of the space that is otherwise occupied by bound retinol in holo-CRBP, and are displaced from these positions on ligand binding. These results indicate that a flexible area encompassing the betaC-betaD and betaE-betaF turns may serve as the ligand portal and that these turns undergo conformational changes associated with the not yet clarified mechanism of retinol binding and release in CRBPs.

Amino Acid Sequence↗

PubMed2000

Effects of abnormal lighting on the development of zebrafish visual behavior.

Studies across several species have demonstrated that the developing visual system is influenced by environmental conditions. This study examined the effects of abnormal lighting environments on zebrafish visual behavior. Zebrafish were raised under different lighting conditions from fertilization to 6 days postfertilization (dpf). These conditions included a normal light/dark cycle, constant dark, constant light, as well as exposure to various lighting cycles with intense light. Visual acuity was tested using the optomotor response to black and white vertical stripes of various widths. The results showed that visual acuity of the normal fish improved with age. In addition, fish raised in constant light had significantly lower visual acuity than fish raised under normal lighting conditions. Subjects raised in constant dark showed somewhat lower visual acuity than normal subjects when tested at 12-14 dpf, but the deficits were not as severe as those found in fish raised in constant light. Intense light rearing did not have any substantial effects on visual development, unless it was constant. In conclusion, under normal conditions, zebrafish visual acuity improves with age, supporting previous work on zebrafish development. In addition, zebrafish visual behavior is altered by abnormal lighting conditions; the most severe decrements occur when raised under constant light.

Animals↗

PubMed2002

Gonadotropin regulation of activin betaA and activin type IIA receptor expression in the ovarian follicle cells of the zebrafish, Danio rerio.

We have previously demonstrated that both activin and its receptors are expressed in the zebrafish ovary, suggesting paracrine roles for activin in the ovarian functions. Activin significantly stimulated zebrafish oocyte maturation in vitro, and this effect could be blocked by follistatin, an activin-binding protein. Interestingly, follistatin also blocked the stimulatory effect of gonadotropin (hCG) on the oocyte maturation. Taken together, these results have led to a hypothesis that the ovarian activin system may play a role in mediating the actions of gonadotropin in the ovary. To test this hypothesis, the present study was undertaken to investigate if gonadotropin has any effect on the expression of activin betaA subunit and activin type IIA (ActRIIA) receptor in the zebrafish ovary. A primary culture of zebrafish ovarian follicle cells was established in the present study, and the cultured cells expressed both activin betaA and ActRIIA receptor when assayed with RT-PCR. The primary culture consisted of three major types of cells, presumably the fibroblasts, the thecal cells and the granulosa cells, according to the morphological features, histochemical staining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and RT-PCR for aromatase. Using a semi-quantitative RT-PCR with beta-actin as the internal control, we demonstrated that hCG significantly stimulated mRNA expression of both activin betaA and ActRIIA receptor in the cultured follicle cells in a time- and dose-dependent manner. Treatment of the cells with hCG quickly increased the steady-state mRNA levels of activin betaA and ActRIIA receptor, and the effect peaked at 2 h of treatment. The stimulatory effect of gonadotropin diminished with longer treatment and no effect was observed at 8 h of treatment. The effect of hCG also exhibited strong dose dependence when assayed at 2 h of treatment. The levels of activin betaA and ActRIIA receptor mRNA elevated with increasing dose of hCG; however, the effect significantly decreased at dosage higher than 15 IU/ml. Consistent with the stimulatory effect of gonadotropin on the expression of activin betaA and ActRIIA receptor, IBMX, forskolin and 8-Br-cAMP all significantly increased the mRNA levels of activin betaA and ActRIIA receptor. These results suggest that gonadotropin activates the activin system in the zebrafish ovary by increasing the expression of both activin and its receptors.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Rapid identification and isolation of zebrafish cDNA clones.

A fast and economical approach, referred to as cDNA clone tagging, was adapted to identify and isolate zebrafish cDNA clones. The basic approach was to partially sequence the coding region of size selected cDNA clones and the partial sequences were then used as tags for identifying the clones through homology search. To benefit maximally from the tagging approach, two cDNA libraries, derived from embryonic and adult fish poly(A)+ RNAs, respectively, were constructed by unidirectional cloning; conceptually, they have the potential to represent all expressed zebrafish genes. A total of 1084 clones were sequenced from the two libraries, and 511 clones were identified, based on sequence homology. These identified clones were derived from at least 261 genes, encoding 48 translational machinery proteins, 47 cytosolic proteins, 43 cytoskeletal proteins, 41 nuclear proteins, 32 membrane proteins, 22 secreted proteins, 20 mitochondrial proteins and 8 proteins with an unknown location. Of the 261 distinct cDNA clones identified, 254 were isolated for the first time in the zebrafish. These tagged cDNA clones, identified and unidentified, provide rich resources for developmental analysis as well as mapping of zebrafish genome. The long-term objective of this study is to establish a tagged zebrafish gene library that can be accessed both by hybridization screening against the plasmid DNAs and by electronic screening using the sequence information.

Animals↗

PubMed2001

A zebrafish homologue of deleted in colorectal cancer (zdcc) is expressed in the first neuronal clusters of the developing brain.

DCC (deleted in colon cancer), Neogenin and UNC-5 are all members of the immunoglobulin superfamily of transmembrane receptors which are believed to play a role in axon guidance by binding to their ligands, the Netrin/UNC-40 family of secreted molecules (Cell. Mol. Life Sci. 56 (1999) 62; Curr. Opin. Genet. Dev. 7 (1997) 87). Although zebrafish homologues of the Netrin family of secreted molecules have been reported, to date there has been no published description of zebrafish DCC homologues (Mol. Cell. Neurosci. 9 (1997) 293; Mol. Cell. Neurosci. 11 (1998) 194; Mech. Dev. 62 (1997) 147). We report here the expression pattern of a zebrafish dcc (zdcc) homologue during the initial period of neurogenesis and axon tract formation within the developing central nervous system. Between 12 and 33 h post-fertilisation zdcc is expressed in a dynamic spatiotemporal pattern in all major subdivisions of the central nervous system. Double-labelling for zdcc and the post-mitotic neuronal marker HNK-1 revealed that subpopulations of neurons within the first nuclei of the zebrafish brain express zdcc. These results support our previous observation that patterning of neuronal clusters in the zebrafish brain occurs early in development (Dev. Biol. 229 (2001) 271).

Amino Acid Sequence↗

PubMed2002

Cloning of two tryptophan hydroxylase genes expressed in the diencephalon of the developing zebrafish brain.

The monoamine serotonin (5-HT) exerts key neuromodulatory activities in all animal phyla, but the development and function of the serotonergic system is still incompletely understood. The zebrafish Danio rerio is an excellent model to approach this question since it is amenable to a combination of genetic, molecular and embryological studies. In order to characterize the organization of serotonergic neurons in the zebrafish we cloned two cDNAs encoding distinct forms of tryptophan hydroxylase (Tph), the rate-limiting enzyme in serotonin synthesis. We report here the pattern of expression of these two genes in relation with immunoreactive TH and 5-HT nuclei in the developing zebrafish embryo and early larva. tphD1 expression starts at 22 h post-fertilization (hpf) in the epiphysis and in basal spinal cells. Expression persists in the epiphysis until at least 4 days (dpf). Between 48 hpf and 3 dpf, tphD1 expression is initiated in retinal amacrine cells and in restricted preoptic and posterior tubercular nuclei within the basal diencephalon. At 3 and 4 dpf, tphD1 expression is newly initiated in the caudal hypothalamus and in branchial arches-associated neurons. tphD2 mRNA is detected transiently (between 30 somites and 32 hpf) in a restricted preoptic nucleus. All sites of tphD1 or D2 expression within the anterior central nervous system are also immunoreactive for 5-HT, but are not positive for TH. However, neither tphD gene is expressed in raphe nuclei, suggesting that additional tph gene(s) exist in zebrafish to account for 5-HT synthesis in that location. The co-expression of tphD1, tphD2 and 5-HT in the zebrafish diencephalon appears in striking contrast to the situation in mammals, where diencephalic serotonin results from re-uptake rather than from local production.

Animals↗

PubMed1997

A zebrafish Id homologue and its pattern of expression during embryogenesis.

We describe the cloning, sequencing and pattern of transcript distribution during embryogenesis of a zebrafish Id homologue that we have called Id6. Transcription of the gene is spatially regulated, and its pattern of transcription shows considerable overlaps with those of other zebrafish genes with homology to Drosophila neurogenic genes, such as Notch and Delta. Since all these genes are coexpressed in particular cells, they may function together in a single genetic circuit in zebrafish as they do in Drosophila. A zebrafish homologue of Drosophila AS-C proteins can activate transcription of a CAT reporter gene by binding to an E-box in mouse 3T3 cells, either alone or in conjunction with ZfE12. The activation of transcription is inhibited in the presence of Id6. This indicates that the zebrafish gene described here is a genuine member of the Id family, and suggests that it may serve a function similar to that of the Drosophila gene emc and mammalian Ids during development.

Amino Acid Sequence↗

PubMed2003

Muscle-specific expression of myogenin in zebrafish embryos is controlled by multiple regulatory elements in the promoter.

Myogenin is a member of the basic Helix-Loop-Helix transcription factor family that play key roles in myoblast specification and differentiation. Myogenin is specifically expressed in developing somite and skeletal muscles in zebrafish embryos. To determine the regulation of myogenin expression, we reported here the characterization of zebrafish myogenin gene and analysis of its promoter activity in zebrafish embryos. Our data showed that a 0.8-kb myogenin promoter was sufficient to direct correct temporal and spatial muscle-specific green fluorescence protein expression in zebrafish embryos. Sequence analysis identified two putative E box sites in the myogenin gene promoter. In addition, a MEF2 recognition site and a MEF3 binding site were also found in the promoter. Mutation of the E boxes, MEF2 or MEF3 binding site individually had little effect on the muscle-specificity and activity of the myogenin promoter. However, mutating these sites in various combinations, e.g. E boxes and MEF2 binding site, or MEF2 and MEF3 sites significantly reduced the activity of the promoter. Moreover, mutating the E boxes, MEF2 and MEF3 sites together almost abolished the activity of the promoter. These data indicate that muscle-specific expression of myogenin in zebrafish embryos is controlled by multiple regulatory elements in the promoter. In addition, because these regulatory elements control myogenin expression in mouse and human embryos, these data suggest that the regulatory mechanism controlling myogenin expression might be conserved during evolution.

Animals↗

PubMed2003

Metabolism of bisphenol A in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) in relation to estrogenic response.

The kinetics of bisphenol A (BPA) were investigated in zebrafish (Danio rerio) exposed to 100 microg BPA/l. BPA uptake was measured during a 7-day period followed by an elimination phase of similar duration. After 2, 6, 12, 24, 48, 72, 120 and 168 h of uptake/elimination, fish were analysed for their content of BPA, bisphenol A glucuronic acid (BPAGA) and bisphenol A sulfate (BPAS). Within the first 24 h steady state levels of BPA, BPAGA and BPAS were reached and the total body concentrations were calculated to be 569, 12,600 and 39.9 ng/g fish, respectively. Elimination rates of the three compounds in zebrafish were estimated by fitting the data to a compartment model. An initial rapid elimination phase was observed for BPA and BPAS with total body half lives (T(1/2)) of <1.1 h and 30 min, followed by a slower second elimination phase with T(1/2) values of 139 and 71 h, respectively. Excretion of BPAGA occurred from a single compartment with a T(1/2) of 35 h. The steady state concentration of BPA and its metabolites were investigated in rainbow trout (Oncorhynchus mykiss) exposed to 100 microg BPA/l. The toxicokinetic parameters from zebrafish and rainbow trout were compared; including previously published data on the rainbow trout. The data indicate that the smaller estrogenic sensitivity observed for the zebrafish may be caused by a more rapid metabolism of BPA in the zebrafish liver.

Animals↗