Abstract: The present invention provides a recombinant plasmid, comprising (a) a ubiquitous promoter, (b) one fluorescent gene, said gene being operably linked to and inserted downstream of said ubiquitous promoter, (c) a skin-specific or muscle-specific promoter, and (d) another fluorescent gene, said gene being operably linked to and inserted downstream of said skin-specific or muscle-specific promoter, wherein the ubiquitous promoter and the skin-specific or muscle-specific promoter have the adverse directional property and the ubiquitous promoter and the skin-specific or muscle-specific promoter are located upstream of said fluorescent gene and said another fluorescent gene respectively so as to have the directional property which permits transcription of said genes. Also provided a host cell, a method of producing a transgenic fish and transgenic fish harboring the plasmid of the invention.

Abstract: The present invention relates to expression control sequences of a vertebrate liver fatty acid binding protein (L-FABP) gene that, when operably linked to a reporter (e.g., a heterologous reporter, such as the green fluorescent protein (GFP)), directly express the reporter in a fashion that mimics the liver-specific development of the L-FABP gene in the vertebrate. Also disclosed is transgenic fish, such as a transgenic zebrafish, whose cells comprises at least one genomically integrated copy of a recombinant construct comprising such an expression control sequence, operably linked to a reporter sequence, so that the expression of the reporter is liver-cell specific, both spatially and temporally during development.

Abstract: The present invention relates to expression control sequences of a vertebrate liver fatty acid binding protein (L-FABP) gene that, when operably linked to a reporter (e.g., a heterologous reporter, such as the green fluorescent protein (GFP)), directly express the reporter in a fashion that mimics the liver-specific development of the L-FABP gene in the vertebrate. Also disclosed is transgenic fish, such as a transgenic zebrafish, whose cells comprises at least one genomically integrated copy of a recombinant construct comprising such an expression control sequence, operably linked to a reporter sequence, so that the expression of the reporter is liver-cell specific, both spatially and temporally during development.

Abstract: The invention provides methods of introducing heterologous cells into fish. After introduction cells remain viable, and in some instances proliferate, for sufficient time to conduct a variety of analyses on the heterologous cells or the fish or both. Such methods are useful for screening potential drugs for toxicity toward introduced cells or for capacity to stimulate differentiation and/or proliferation of introduced cells. Such methods are also useful for diagnosing the presence of small quantities of cancerous cells or pathogens in patient tissue samples. Such methods are also useful for culturing cells for subsequent use in cell or tissue engineering.

Abstract: The present invention is directed a Lef1/&bgr;-catenin-dependent reporter and to transgenic fish containing this reporter. The present invention is also directed to the use of the reporter and the transgenic fish as a model for the &bgr;-catenin signaling pathway. The model is useful for identifying genes in the &bgr;-catenin signaling pathway and for identifying drugs that can modulate the &bgr;-catenin signaling pathway. Such drugs are useful for treating or preventing melanoma, colorectal cancer and osteoporosis, among other disease conditions.

Abstract: Methods for preparing cells that contain artificial chromosomes, methods for preparation of artificial chromosomes, methods for purification of artificial chromosomes, methods for targeted insertion of heterologous DNA into artificial chromosomes, and methods for delivery of the chromosomes to selected cells and tissues are provided. Also provided methods for producing transgenic plants and animals using the artificial chromosomes and the resulting transgenic organisms are provided.

Abstract: The present invention relates to zebrafish models for the screening of compounds and genes that target angiogenesis in an in vivo model system.

Abstract: Four zebrafish gene promoters, which are skin specific, muscle specific, skeletal muscle specific and ubiquitously expressed respectively, were isolated and ligated to the 5′ end of the EGFP gene. When the resulting chimeric gene constructs were introduced into zebrafish, the transgenic zebrafish emit green fluorescence under a blue light or ultraviolet light according to the specificity of the promoters used. Thus, new varieties of ornamental fish of different fluorescence patterns, e.g., skin fluorescence, muscle fluorescence, skeletal muscle-specific and/or ubiquitous fluorescence, are developed.

Abstract: Compositions and methods for conferring enhanced disease resistance in a fish are provided. Compositions include novel recombinant constructs that induce transgenic expression of anti-pathogenic polypeptides, including cecropin proteins or biologically active variants thereof, in a fish. Expression of the anti-pathogenic polypeptide is under the control of novel synthetic promoters, naturally occurring fish promoters, or biologically active variants thereof. Compositions of the invention also include transgenic fish cells, fish eggs, and fish, particularly catfish, having the recombinant constructs of the invention stably integrated within their genome. Methods for expressing a polypeptide of interest within a host cell are also provided, wherein expression is under control of the synthetic promoters of the invention.

Abstract: (1) Transgenic medaka fish into which a polynucleotide having the nucleotide sequence from 211 to 1935 position represented by Sequence ID No: 1 is introduced, (2) A method of producing medaka fish having one or more thrombi, comprising the step of raising the transgenic medaka fish described in (1) in the presence of estrogen, (3) Medaka fish having one or more thrombi produced by the method described in (2), and (4) A method of testing an estrogen-like acting substance, comprising the steps of raising the transgenic medaka fish described in (1) in test water, and observing whether or not one or more thrombi are formed in the medaka fish after the raising step.

Abstract: The invention relates to a recombinant DNA method for producing transgenic golden zebrafish (golden zebra danio). The invention also relates to novel gene fragments for producing the transgenic golden zebrafish. The invention further relates to novel transgenic golden zebrafish.

Abstract: The present invention provides transgenic fish whose genome has stably-integrated therein an oncogene operably linked to a promoter. Methods of making the transgenic fish and methods for their use are also provided. In one embodiment, the transgenic fish may advantageously be utilized in methods of screening for drugs or agents that modulate oncogene-mediated neoplastic or hyperplasic transformation, or that modulate sensitivity to chemotherapy or radiation therapy. In another embodiment, the transgenic fish may be used methods of identifying mutations that modulate oncogene-mediated neoplastic or hyperplastic transformation, or that modulate sensitivity to chemotherapy or radiation therapy.

Abstract: The present invention provides a system and method for providing and using quality control information pertaining to a cell culture. The system includes a chamber (106) containing the cell culture (104) and a unique identifier (116) disposed on the chamber (106) corresponding to a data file (114) containing the quality control information pertaining to the cell culture before an event. One method includes obtaining quality control information from the microelectrode array before the event (132), storing the quality control information in a data file (134), associating a unique identifier with the microelectrode array that corresponds to the data file (136), and providing access to the data file via the unique identifier after the event (138).

Abstract: The present invention concerns transgenic vertebrates that are useful in expressing proteins and in producing antibodies. The present invention discloses methods for producing vertebrates that are transgenic for a bacteriophage RNA polymerase. The present invention further discloses methods for the use of such transgenic vertebrates in protein expression and in antibody production.

Abstract: This invention relates to a see-through medaka deficient in iridophores, melanophores, xanthophores and leucophores; a see-through medaka deficient in iridophores, melanophores and xanthophores, and whose sex can be identified by the presence or absence of leucophores and/or a DNA marker; and a see-through medaka wherein a specific organ is allowed to produce luminescence by introducing a hybrid gene being a fusion of a promoter of a gene expressing specifically in that organ and a coding region of a gene encoding a fluorescent protein.

Abstract: The present invention relates to a zebrafish HuC promoter with its 5′-flanking region which directs the neuron-specific expression of structural genes, a transgenic animal that shows the neuron-specific expression of GFP (green fluorescence protein) under the regulation of the HuC promoter, and a method for screening neurogenesis mutants in zebrafish by use of the transgenic animal. The HuC promoter with its 5′-flanking region can be used in the study of the regulatory mechanism responsible for the differentiation of the nervous system. Additionally, the HuCP-GFP transgenic zebrafish enables the direct identification of neurogenesis and axonogenesis, as well as being a valuable tool for isolating and analyzing neurogenesis mutants in live zebrafish with ease.

Abstract: The invention features novel zebrafish nucleic acid and amino acid molecules, and zebrafish containing mutations in important developmental genes. In addition, the invention features the use of these nucleic acid and amino acid molecules in methods of diagnosing, preventing, and treating a variety of mammalian diseases and developmental disorders. Furthermore, zebrafish mutant for a nucleic acid or amino acid molecule of the invention may be used in screens for compounds that modulate the development of an organism as a whole or of specific tissues or organs within an organism. In particular, the present invention features novel nucleic acid sequences involved, e.g., in kidney development and kidney disorders. Mutations in these sequences, for example, result in the formation of cysts in the kidney.

Abstract: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided. The invention further provides high throughput methods of screening agents in multi-well plates.

Abstract: A substantially purebred non-transgenically developed fish produced by selecting fish having at least one desirable trait from a population of same species fish and preparing a DNA fingerprint of the selected fish so as to be able to identify breeder fish by use of selected microsatellite loci identified as being associated with fish having the at least one desired trait, breeding the selected breeder fish to produce offspring having the at least one desired trait. Also provided is a method for producing the substantially purebred non-transgenically developed fish.

Abstract: A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the animal is provided. Also provided are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-8. The animals so treated are characterized by increased muscle tissue and bone content.

Abstract: The present invention provides an antifreeze protein, wherein thermal hysteresis activity and ice recrystallization inhibitory activity are artificially improved.

Abstract: An engineered mutant teleost embryo having reduced flt1 activity that causes a phenotype of normal assembly of main circulatory routes and a reduction in sprouted blood vessels is described. Methods of using the mutant teleost embryo for identifying genes that interact with flt1 are also described.

Abstract: The invention provides methods and materials related to modulating syndecan levels and angiogenesis in an animal. The invention provides syndecan polypeptides and nucleic acids encoding syndecan polypeptides. The invention also provides polynucleotides and polynucleotide analogues for modulating angiogenesis, as well as cells and embryos containing the polynucleotides and polynucleotide analogues. The invention further provides methods for identifying syndecan- and angiogenesis-modulating agents.

Abstract: The present invention relates to methods for producing transgenic animals. Specifically, the methods of the present invention include production of a transgenic animal by transgenic intracytoplasmic sperm injection, retroviral gene transfer, intracytoplasmic nuclear injection, and pronuclear injection. In addition, the present invention also relates to methods for using transgenic animals as models for human disease and diagnosis. In particular, these transgenic animals may be used as models for embryo and fetal development, as models to assess the safety and efficacy of drug therapy and gene therapy, and as models for disease diagnosis. The methods of the present invention are also directed to methods of using transgenic embryonic cells to treat human diseases.

Abstract: The application is related to the field of nucleic acids with identified utility, and more particularly, to genes, related nucleic acids, their complements, polypeptides, and methods of using the same for blood vessel, cartilage, and bone formation, as well as inhibition thereof. The application describes discoveries made using the zebrafish embryo technique, as well as other techniques that are described herein. The discoveries include genes, related nucleic acids, and their complements, as well as sequences, polypeptides, other molecules, and methods for using them, e.g., TDE1, PTV, MOESIN, and HKE4. Also described are polypeptide products, inhibition of expression, administration of materials and products, screening procedures, and techniques for making drugs. Moreover, uses of these discoveries in appropriate contexts are set forth.

Abstract: Polycation-sensing receptors present in aquatic species and methods of regulating polycation-sensing receptor-mediated functions in aquatic species are described.

Abstract: The present invention is directed to methods of making a fish embryo cell line that can give rise to germ cells when introduced to a fish embryo. The present invention is further directed to methods of using the fish embryo cell line, making germ line chimeric fish, and to a cell culture medium.

Abstract: The invention relates to methods, cells and nucleic acids for making transgenic animals. The methods generally comprise introducing into a genome of an animal a genetic construct comprising a transcriptional regulatory element operably linked to a heterologous marker gene encoding a marker, wherein the element drives expression of the marker across genera transgenic in the construct sufficient to visually detect the marker in photoreceptive cells or organs, and selecting for transgenesis by visually detecting the marker in a photoreceptive cell or organ of the animal.

Abstract: A transgenic screen and method for screening biological and chemical test substances or molecules for their ability to influence or modulate the production of BDNF in cells, includes a fusion gene having a zebrafish BDNF gene fragment (promoter) and a fluorescent marker gene inserted downstream of the BDNF gene fragment. When the fusion gene is injected into a zebrafish embryo, the BDNF promoter causes the production of fluorescent protein in various cell types. The embryo is exposed to a test substance for determining the effect thereof on the production of the fluorescent marker protein.

Abstract: Disclosed herein are an isolated polynucleotide comprising a lectin gene regulation site of a mud loach, expressed as SEQ ID NO: 1, an expression vector comprising a lectin gene regulation site of a mud loach, an expression vector comprising a lectin gene regulation site of a mud loach and a growth hormone gene of a mud loach, and an expression vector comprising a lectin gene regulation site of a mud loach and a growth hormone gene of a carp. Also provided a method of making a transgenic mud loach or carp comprising microinjecting the expression vector of a growth hormone gene into fertilized eggs of a mud loach or carp and culturing the eggs such that the eggs hatch and result in a mud loach or carp fish which expresses the growth hormone gene at levels which increase the rate of growth of the fish relative to wild-type mud loach or carp, and a mud loach or carp transformed with the expression vector.

Abstract: The present invention utilizes fluorescent lipids, particularly quenched phospholipid or cholesterol analogues, to facilitate screening for phenotypes representing perturbations of lipid processing; screening for genetic mutations that lead to disorders of phospholipid and/or cholesterol metabolism; and screening of compounds designed to treat disorders of phospholipid and/or cholesterol metabolism.

Abstract: The present invention concerns a method for in vivo generation of a linear polynucleotide with 5′ and 3′ free ends from a vector having no free end, said linear polynucleotide being integrated into the host cell genome. The vector having no free end according to the present invention comprise the polynucleotide to be linearized or excised flanked by a cleavage site, said cleavage site being preferably not found in the host cell genome. The present invention also relates to the resulting cells and their uses, for example for production of proteins or other genes, biomolecules, biomaterials, transgenic plants, vaccines, transgenic animals or for treatment or prophylaxis of a condition or disorder in an individual.

Abstract: The present invention relates to the clonal propagation of primate offspring by embryo splitting. Here, genetically identical nonhuman embryos may be produced as twin and larger sets by separation and reaggregation of blastomeres of cleavage-stage embryos. Furthermore, the present invention also relates to methods for producing embryonic stem cells and transgenic embryonic stem cells isolated from dissociated blastomeres.

Abstract: The invention relates to new fish growth hormones, nucleic acids encoding them, and transgenic fish that express them.

Abstract: The present invention provides nucleic acid and polypeptide sequences associated with teleost ERG genes, which encode ERG family potassium channels. The invention further provides teleost models for cardiac function and methods of screening for cardio-active agents using mutant teleost larvae having reduced teleost ERG activity.

Abstract: The present invention encompasses three full length nucleic acid and amino acid sequences for PolyValent Cation-Sensing Receptors (PVCR) in Atlantic Salmon. These PVCR have been named SalmoKCaR#1, SalmoKCaR#2, and SalmoKCaR#3. The present invention includes homologs thereof, antibodies thereto, and methods for assessing SalmoKCaR nucleic acid molecules and polypeptides. The present invention further includes plasmids, vectors, host cells containing the nucleic acid sequences of SalmoKCaR #1,2 and/or 3.

Abstract: The invention relates to an animal model for studying behavior related to fatty acid amide and hydrolysis of fatty acid amide. The invention provides transgenic animals in which the protein fatty acid amide hydrolase is not expressed, and methods of using such animals.

Abstract: The present invention relates to zebrafish models for neurodegenerative disorders that allow screening of compounds for their ability to protect and/or regenerate neurons in vivo in a whole vertebrate organism. The present invention also provides methods of identifying gene targets for neuroprotective compounds, compounds that regenerate neurons and compounds that promote neurogenesis.

Abstract: Disclosed are transgenic fish, and a method of making transgenic fish, which express transgenes in stable and predictable tissue- or developmentally-specific patterns. The transgenic fish contain transgene constructs with homologous expression sequences. Also disclosed are methods of using such transgenic fish. Such expression of transgenes allow the study of developmental processes, the relationship of cell lineages, the assessment of the effect of specific genes and compounds on the development or maintenance of specific tissues or cell lineages, and the maintenance of lines of fish bearing mutant genes.

Abstract: In accordance with the present invention, there are provided humanized fish insulin genes. Humanized insulin the present invention encode human insulin alpha and/or beta chains while using fish-preferred codons and regulatory sequences. These humanized genes are thus expressible in fish islet cells. Also provided are transgenic fish having islet cells containing and capable of expressing humanized insulin genes. These islet cells (Brockmann Bodies) can be xenotransplanted into subjects having diabetes. In this manner normoglycemia can be achieved in the recipient of the islets.

Abstract: The present invention utilizes fluorescent lipids, particularly quenched phospholipid or cholesterol analogues, to facilitate screening for phenotypes representing perturbations of lipid processing; screening for genetic mutations that lead to disorders of phospholipid and/or cholesterol metabolism; and screening of compounds designed to treat disorders of phospholipid and/or cholesterol metabolism. The present invention is a mutant fish containing a metabolic defect affecting phospholipid and cholesterol processing. The mutant fish is useful for studying phospholipid and cholesterol metabolism and for screening compounds designed to treat disorders of phospholipid and/or cholesterol metabolism.

Abstract: The present invention provides transgenic fish whose somatic and germ cells contain a genomically integrated plasmid containing a heterologous mutation target nucleic acid sequence that is detectable via bioassay in a bacterial cell into which the target nucleic acid has been introduced. The frequency and character of mutations in the mutatable target nucleic acid sequence following exposure of the transgenic fish to one or more potentially mutagenic agents can thus be evaluated.

Abstract: A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-8. The animals so treated are characterized by increased muscle tissue.

Abstract: The present invention provides fish system as a powerful forward genetic tool to directly identify a number of novel genes involved in cell proliferation in vertebrates without the time consuming and costly maintenance of animals. The invention provides a tool to identify functional characteristics of a protein without prior knowledge of the gene sequence. After identification of the mutant gene in the fish system, the nucleic acid sequence of the gene can be used for identifying a homologue of the gene in another species, for example, in humans.

Abstract: (1) Transgenic medaka fish into which a polynucleotide having the nucleotide sequence from 211 to 1935 position represented by Sequence ID No: 1 is introduced, (2) A method of producing medaka fish having one or more thrombi, comprising the step of raising the transgenic medaka fish described in (1) in the presence of estrogen, (3) Medaka fish having one or more thrombi produced by the method described in (2), and (4) A method of testing an estrogen-like acting substance, comprising the steps of raising the transgenic medaka fish described in (1) in test water, and observing whether or not one or more thrombi are formed in the medaka fish after the raising step.

Abstract: The present invention relates generally to novel methods of producing transgenic chickens that generate antibodies or immunoglobulin polypeptides in whites of eggs. More specifically, one embodiment of the present invention relates to methods of inserting immunoglobulin-encoding transgenes into avian sperm cells for transfer to ova to generate transgenic zygotes. The transgenes may include at least two immunoglobulin-encoding nucleic acid sequences and an internal ribosome entry site (IRES) that allow the immunoglobulin polypeptides to be expressed by chicken cells and hence in egg whites.

Abstract: The present invention relates to transgenic animals expressing a hypersensitive nicotinic acetylcholine receptor. Transgenic animals have point mutations in the nucleic acid sequence encoding the &agr;4 subunit of the receptor that result in increased sensitivity to nicotine. Such transgenic animals are model systems for nicotine addiction and certain types of epilepsy.

Abstract: The invention relates to an animal model for studying behavior related to RGS9 and RGS9 modulated dopamine D2-mediated behavior. The invention provides transgenic non-human animals in which RGS9 expression is disrupted, methods of using such animals, and methods of modulating dopamine D2-mediated behavior.

Abstract: The invention provides sequence specific polynucleotide analogues and methods for determining the function of a nucleic acid of known sequence.

Abstract: Disclosed are transgenic fish, and a method of making transgenic fish, which express transgenes in stable and predictable tissue- or developmentally-specific patterns. The transgenic fish contain transgene constructs with homologous expression sequences. Also disclosed are methods of using such transgenic fish. Such expression of transgenes allow the study of developmental processes, the relationship of cell lineages, the assessment of the effect of specific genes and compounds on the development or maintenance of specific tissues or cell lineages, and the maintenance of lines of fish bearing mutant genes.