Functional validation of ABHD12 mutations in the neurodegenerative disease PHARC.

ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare, progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise functional role(s) leading to PHARC disease had not previously been characterized. Cell and zebrafish models were designed to demonstrate the causal link between an identified new missense mutation p.

Triiodothyronine-induced changes in the zebrafish transcriptome during the eleutheroembryonic stage: implications for bisphenol A developmental toxicity.

Thyroid disruption during early development is a current matter of concern due to its significant human health implications. We present here a transcriptome analysis of thyroid hormone-regulated genes in zebrafish during the eleutheroembryonic stage (days 2-5 post fertilization) to detect potential markers of thyroid disruption. Exposure to 3,5,3'-triiodo-l-thyroxine (T3, 50 nM) induced changes in a minor portion (less than 2%) of the zebrafish transcriptome, with a significant fraction of genes involved in the haematopoietic system, eye formation, and ossification/skeletal system, including the thyroid receptor thra gene.

Vitellogenin expression in white adipose tissue in female teleost fish.

In most oviparous animal species, oocyte growth occurs via the uptake of plasma egg yolk precursors, predominantly vitellogenins (Vtg). These glycolipoproteins are members of the large lipid transfer protein superfamily and key players in reproduction. While the vertebrate liver has been demonstrated to synthesize large amounts of Vtg, mostly under 17beta-estradiol control, the ability of other tissues to express significant amounts of Vtg has not been conclusively demonstrated.

Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish.

Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish.

High transcript level of fatty acid-binding protein 11 but not of very low-density lipoprotein receptor is correlated to ovarian follicle atresia in a teleost fish (Solea senegalensis).

Transcripts encoding a fatty acid-binding protein (FABP), Fabp11, and two isoforms of very low-density lipoprotein receptor (Vldlr; vitellogenin receptor) were characterized from the ovary of Senegalese sole (Solea senegalensis). Phylogenetic analyses of vertebrate FABPs demonstrated that Senegalese sole Fabp11, as zebrafish (Danio rerio) homologous sequences, is part of a newly defined teleost fish FABP subfamily that is a sister clade of tetrapod FABP4/FABP5/FABP8/FABP9. RT-PCR revealed high levels of vldlr transcript splicing variants in the ovaries and, to a lesser extent, in somatic tissues, whereas fabp11 was highly expressed in the ovaries, liver, and adipose tissue.

Conserved expression of alternative splicing variants of peroxisomal acyl-CoA oxidase 1 in vertebrates and developmental and nutritional regulation in fish.

The acyl-coenzyme A oxidase 1 (ACOX1) catalyzes the first, rate-limiting step in peroxisomal beta-oxidation of medium to very long straight-chain fatty acids. Zebrafish (Danio rerio) acox1 was characterized and compared with homologs from other sequenced genomes, revealing a remarkable conservation of structure in the vertebrate lineage. Strictly conserved regions of the deduced proteins included acyl-CoA oxidase and FAD binding domains, as well as a COOH-terminal peroxisomal targeting signal.

Epidermal transient down-regulation of retinol-binding protein 4 and mirror expression of apolipoprotein Eb and estrogen receptor 2a during zebrafish fin and scale development.

Very little is known about the molecular control of skin patterning and scale morphogenesis in teleost fish. We have found radially symmetrical epidermal placodes with down-regulation of retinol-binding protein 4 (rbp4) expression during the initial paired fin and scale morphogenesis in zebrafish (Danio rerio). This finding may be related to changes in keratinocyte cytodifferentiation and/or the integument retinoid metabolism.

Molecular phenotype of zebrafish ovarian follicle by serial analysis of gene expression and proteomic profiling, and comparison with the transcriptomes of other animals.

Background: The ability of an oocyte to develop into a viable embryo depends on the accumulation of specific maternal information and molecules, such as RNAs and proteins. A serial analysis of gene expression (SAGE) was carried out in parallel with proteomic analysis on fully-grown ovarian follicles from zebrafish (Danio rerio). The data obtained were compared with ovary/follicle/egg molecular phenotypes of other animals, published or available in public sequence databases.

Molecular characterization, phylogenetic relationships, and developmental expression patterns of prion genes in zebrafish (Danio rerio).

Prion diseases are characterized by the accumulation of a pathogenic misfolded form of a prion protein (PrP) encoded by the Prnp gene in humans. In the present study in zebrafish, two transcripts and the corresponding genes encoding prion proteins, PrP1 and PrP2, related to human PrP have been characterized with a relatively divergent deduced amino acid sequence, but a well preserved overall organization of structural prion protein motifs. Whole-mount in situ hybridization analysis performed during embryonic and larval development showed a high level of PrP1 mRNA spatially restricted to the anterior floor-plate of the central nervous system and in ganglia.

Developmental expression and nutritional regulation of a zebrafish gene homologous to mammalian microsomal triglyceride transfer protein large subunit.

The microsomal triglyceride transfer protein (MTP) large subunit is required for the assembly and secretion of apolipoprotein B-containing lipoproteins. We have found a zebrafish mtp homologous gene coding a protein with 54% identity with human MTP large subunit with the most conserved regions distributed in the corresponding predicted alpha-helical and C- and A-sheet domains. In situ hybridizations showed that zebrafish mtp transcripts were distributed in the yolk syncytial layer during early embryogenesis and in anterior intestine and liver from 48 hr postfertilization onward.

Expression patterns of three estrogen receptor genes during zebrafish (Danio rerio) development: evidence for high expression in neuromasts.

The estrogen receptor (ER) genes encode a group of nuclear enhancer proteins, which are important ligand-activated transcription factors, modulating estrogen-target gene transcription. In this study we analyzed expression patterns of three zebrafish ER genes, esr1, esr2a, and esr2b, during development using whole-mount in situ hybridization. High levels of esr2a and esr2b of maternal origin are inherited and segregated to the blastomers.