Abstract: This invention describes a novel method of agricultural animal production that provides animals with optimum growth characteristics in a reliable and cost-effective manner. The invention utilizes a novel combination of Nuclear Transfer (NT) and Embryonic Stem (ES) cell technologies that improves the efficiency of delivering optimized animals and facilitates the introduction of genetic modifications into farm animals.

Abstract: This invention provides vectors and methods for the stable introduction of exogenous nucleic acid sequences into the genome of avians in order to express the exogenous sequences to alter the phenotype of the avians or to produce desired proteins. In particular, transgenic avians are produced which express exogenous sequences in their oviducts and which deposit exogenous proteins into their eggs. Avian eggs that contain exogenous proteins are encompassed by this invention. The instant invention further provides novel forms of interferon and erythropoietin which are efficiently expressed in the oviduct of transgenic avians and deposited into avian eggs.

Abstract: This invention provides vectors and methods for the stable introduction of exogenous nucleic acid sequences into the genome of avians in order to express the exogenous sequences to alter the phenotype of the avians or to produce desired proteins. In particular, transgenic avians are produced which express exogenous sequences in their oviducts and which deposit exogenous proteins into their eggs. Avian eggs that contain exogenous proteins are encompassed by this invention. The instant invention further provides novel forms of interferon and erythropoietin which are efficiently expressed in the oviduct of transgenic avians and deposited into avian eggs.

Abstract: The invention concerns methods for the development of mutant animals, including genetically engineered animals and those carrying spontaneous mutations, as human disease models. In particular, the invention provides an integrated technology, including rigorous specifications and quality control, for the development of animal models that can serve as a living assay system, useful in biomedical research and in the development of human therapeutics.

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: A composition that contains a gamete or an embryo and animal white yolk is disclosed. Also disclosed are applications of the composition.

Abstract: A transgenic non-human animal expressing heparanase from a transgene, methods for its preparation, compositions-of-matter derived therefrom and uses thereof.

Abstract: This invention includes methods for producing non-human mammals expressing monoclonal or oligoclonal B or T lymphocytes, as well as embryonic and hematopoietic stem cells that differentiate into monoclonal or oligoclonal B or T cells, using cloning by nuclear transfer with a B or T cell of interest as the nuclear donor cell.

Abstract: A transgenic chicken is disclosed having disrupted endogenous immunoglobulin production. In one embodiment, a targeting construct is stably integrated into the genome of the chicken by homologous recombination in embryonic stem cells, and injection of the engineered embryonic stem cells into recipient embryos, thereby knocking out the endogenous immunoglobulin gene locus in resulting animals. The targeted disruption of the locus in embryonic stem cells is particularly useful in combination with the insertion of genetic elements encoding exogenous immunoglobulin molecules. After these chickens are cross-bred, a line of chickens is produced that has a reduction of endogenous immunoglobulin molecule production.

Abstract: A recombinant nucleic acid is provided having an avian promoter. One embodiment of the present invention contemplates the use of a gut-specific promoter, wherein a promoter can be the chicken intestinal fatty acid binding protein promoter region. A method for making a transgenic bird is also disclosed by transfecting a bird with a vector comprising a recombinant nucleic acid comprising a chicken intestinal fatty acid binding protein promoter region operably linked to a heterologous nucleic acid expressing a desired polypeptide to be expressed in the gut tissue of an avian.

Abstract: The present invention provides improved methods of injecting an avian egg containing an embryo, preferably an early embryo (e.g., a blastoderm). The methods of the invention may be used to deliver a substance to an egg, remove a sample from an egg, and/or to insert a detector device into an egg to collect information therefrom. In preferred embodiments, the invention is used to deliver a substance to the embryo in ovo. In other preferred embodiments, the invention is used to produce chimeric or transgenic avian embryos in ovo.

Abstract: Sustained cultures of avian embryonic stem cells are provided. Injection of avian embryonic stem cells into recipient embryos yields chimeras with a significant contribution from the embryonic stem cell phenotype. Transgene encoding exogenous proteins are stably integrated in the embryonic stem cells and are present in the somatic tissue of the resulting chimeras. The transgenes may encode exogenous proteins expressed in endodermal, ectodermal, mesodermal, or extra embryonic tissue. Breeding the resulting chimera yields transgenic birds whose genome is comprised of exogenous DNA.

Abstract: Transgenes encoding exogenous proteins are stably integrated into embryonic stem cells and are present in the somatic tissue of transgenic or chimeric birds. The transgenes encode exogenous proteins and are expressed in any of endodermal, ectodermal, mesodermal, or extra embryonic tissue. Tissue specificity is provided by selecting the content of the transgene accordingly. Transgenic birds whose genome is comprised of trangene derived exogenous DNA express exogenous proteins with tissue specificity, and specifically express exogenous proteins in the tubular gland cells of the oviduct to concentrate exogenous proteins in egg white..

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-11 (GDF-11) 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-11. The animals so treated are characterized by increased muscle tissue and bone tissue.

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 method of altering the phenotype of a bird comprises introducing a DNA sequence into somatic cells of a bird contained within an egg during in ovo incubation. The DNA sequence is selected to be effective to cause a change in phenotype, such as an increase in growth rate, feed efficiency, or both in the bird after hatch. A DNA sequence may further be selected to increase disease resistance or induce disease prevention by the expression of an antigen over a period of time.

Abstract: The present invention provides novel isolated nucleic acids comprising an avian nucleic acid sequence encoding a lysozyme gene expression control region. The isolated nucleic acid of the present invention is useful for reducing the chromosomal positional effect of a transgene operably linked to the lysozyme gene expression control region and transfected into a recipient cell and allows expression of an operably linked heterologous nucleic acid insert in a transfected avian cell such as, for example, an oviduct cell. The isolated avian lysozyme of the present invention may be operably linked with a selected nucleic acid insert encoding a polypeptide desired to be expressed in a transfected cell. The recombinant DNA of the present invention may further comprise a polyadenylation signal sequence or a chicken lysozyme 3′ domain.

Abstract: The present invention provides novel isolated nucleic acids comprising an avian nucleic acid sequence encoding an ovomucoid gene expression control region. The ovomucoid promoter region of the present invention allows expression of an operably linked heterologous nucleic acid insert in a transfected cell such as, for example, an avian oviduct cell. The isolated avian ovomucoid promoter of the present invention may be operably linked with a selected nucleic acid insert, wherein the nucleic acid insert encodes a polypeptide desired to be expressed in a transfected cell. The recombinant DNA of the present invention may further comprise a polyadenylation signal sequence. The present invention further includes expression vectors comprising an isolated avian ovomucoid gene expression control region of the present invention, and transfected cells and transgenic avians comprising the expression vectors.

Abstract: This invention provides methods for the stable introduction of heterologous coding sequences into the genome of a bird and expressing the coding sequences to produce desired proteins or to alter the phenotype of the bird. The present invention provides preferred methods for introducing a transgene into the cytoplasm of avian embryonic cells by cytoplasmic microinjection. The embryo then develops into a transgenic adult capable of expressing a heterologous protein and/or capable of generating a line of transgenic birds through breeding. Synthetic vectors and gene promoters useful in the methods are also provided by the present invention, as are transgenic birds that express heterologous protein and avian eggs containing heterologous protein.

Abstract: A culture system for producing PGCs or EG cells by culturing PGCs for long periods in tissue culture is provided. This culture system uses LIF, bFGF, IGF and SCF. The resultant EG cells are useful for the production of transgenic and chimeric avians, in particular, chickens and turkeys, and also for cloning purposes.

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 present invention relates to methods for producing transgenic animals, particularly transgenic birds and fish, using retroviral constructs engineered to carry the transgene(s) of interest.

Abstract: A gene is transferred to the early stage chicken embryo by electroporation with placing the electrode tips to hold both ends of the embryo. Transfer of the desired gene to the early stage embryo was detected using the &bgr;-galactosidase gene of E coli as a reporter gene. The expression of the gene in the early stage embryo of chicken was thus confirmed. This method for transferring a gene into undifferentiated cells is simple to implement, highly efficient in transferring a gene, and applicable to various animal species.

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 and bone content.

Abstract: Vectors and methods are provided for introducing genetic material into cells of a chicken or other avian species. More particularly, vectors and methods are provided for transferring a transgene to an embryonic chicken cell, so as to create a transgenic hen wherein the transgene is expressed in the hen's oviduct and the transgene product is secreted in the hen's eggs and/or those of her offspring. In a preferred embodiment, the transgene product is secreted in the egg white.

Abstract: Growth is improved by utilizing growth enhancement potential methodology to administer a nucleic acid sequence, such as GHRH or an analog, to a female animal, preferably through a parenteral route of administration. Piglets born from sows injected with DNA encoding GHRH are larger, and effects are demonstrated in subsequent pregnancies without additional administration(s) of the vector.

Abstract: A food product and method for treating and preventing diarrhea in a subject animal suffering from or susceptible to diarrhea. The method comprises administering an egg product to the subject animal wherein the egg product is obtained from a hyperimmunized avian.

Abstract: The present invention provides relates to a process to produce egg yolk antibodies binding to small molecule organochlorine pesticides, by periodic immunization of the poultry birds with a desired hapten-protein conjugate in the breast muscle. Antibodies are harvested from egg yolk after five weeks interval.

Abstract: The present invention relates to methods for isolating primordial germ cells (PGCs) from the blastoderm of a stage X avian embryo. The present invention further relates to methods for producing a transgenic bird by modifying the isolated PGCs, such that the cells incorporate at least one transgene into their genetic material; transferring the modified PGCs into a suitable recipient, such as a blastoderm of an avian embryo, hatching the embryo; and testing for the presence of the transgene or expression of the protein encoded by the transgene.

Abstract: The present invention is to provide a chicken LIF gene. Based on this genetic information, LIF protein derived from the chicken can be stably supplied and it solves the problems of the creation of transgenic chickens in the past. In addition, the present invention provides not only transgenic chickens for testing purposes but also supplies the first practical transgenic stock animals. The present invention relates to leukemia inhibitory factor (LIF) shown in sequence No. 2, and the gene that encodes thereof shown in sequence No. 1, and a manufacturing method of chicken LIF. In addition, the present invention pertains to a differential preventer of the chicken differentiable cell, and a method of chicken differential prevention and a culturing method for the chicken differentiable cell using thereof, and a medium comprising thereof.

Abstract: The present invention pertains to a method for treating obesity in a mammal which comprises reducing the biological activity of HMGI genes in the mammal. In another embodiment, the invention pertains to a method for treating a tumor in a patient by reducing the biological activity of normal HMGI genes which comprises administering to the patient a therapeutically effective amount of an inhibitor compound active against normal HMGI-C or HMGI(Y) genes. In another embodiment, the invention pertains to a method of producing a transgenic non-human mammal, the germ cells and somatic cells of which contain an inactivated HMGI gene sequence introduced into the mammal at an embryonic stage. In another embodiment, the invention pertains to a method for screening candidate compounds capable of inhibiting the biological activity of normal HMGI proteins. In another embodiment, the invention pertains to a method for screening candidate compounds capable of inhibiting the biological activity of normal HMGI genes.

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: This invention provides experimental animals suffering corneal epithelial damages, such as dry eye, and methods of using the same to assay a variety of compounds for evaluating the therapeutic effect thereof on said disease, and medicine selected using said method, wherein said corneal epithelial damage is induced by the steps of: using a water-absorbing material having a physical state selected from powder, solution, gel, jelly and tablet, and contacting the said absorbing material with the ocular cornea to generate a difference in osmotic pressure between the inside and outside of ocular corneal epithelium cells.

Abstract: A method of altering the phenotype of a bird comprises introducing a DNA sequence into somatic cells of a bird contained within an egg during in ovo incubation. The DNA sequence is selected to be effective to cause a change in phenotype, such as an increase in growth rate, feed efficiency, or both in the bird after hatch. A DNA sequence may further be selected to increase disease resistance or induce disease prevention by the expression of an antigen over a period of time.

Abstract: An isolated polypeptide comprising an amino acid sequence having at least 80% sequence identity to one or both of SEQ ID NOS:2 or 4, polynucleotides encoding these polypeptides, and antibodies to the polypeptides are useful in treating cancers.

Abstract: The present invention provides novel isolated nucleic acids comprising an avian nucleic acid sequence encoding a lysozyme gene expression control region. The isolated nucleic acid of the present invention is useful for reducing the chromosomal positional effect of a transgene operably linked to the lysozyme gene expression control region and transfected into a recipient cell and allows expression of an operably linked heterologous nucleic acid insert in a transfected avian cell such as, for example, an oviduct cell. The isolated avian lysozyme of the present invention may be operably linked with a selected nucleic acid insert, wherein the nucleic acid insert encodes a polypeptide desired to be expressed in a transfected cell. The nucleic acid insert may be placed in frame with a signal peptide sequence, whereby translation initiation may start with the signal peptide and continue through the nucleic acid insert, thereby producing an expressed polypeptide having the desired amino acid sequence.

Abstract: A transgenic animal expressing heparanase from a transgene, methods for its preparation, compositions-of-matter derived therefrom and its uses.

Abstract: Disclosed is a nucleic acid construct comprising a murine SOCS-3 promoter sequence having SEQ ID NO. 1, or a non-murine homologue thereof, or an operative fragment or derivative The construct can also contain, operatively linked to the SOCS-3 promoter, a gene encoding any preselected protein, and optionally contains a reporter gene to facilitate detection and/or selection of successfully transfected cells.

Abstract: The present invention concerns the use of chromosomal replacement techniques in the context of producing cloned and transgenic animals, in order to correct chromosome abnormalities or alter autosomal genotypes, and provide for novel breeding pairs by replacing the sex chromosome in animals to be cloned. Replacement of a sex chromosome, or an X or Y chromosome, will result in animals that are autosomally isogenic and sexually non-isogenic (AISN), with “autosomally isogenic” meaning that the paired sets of autosomes (non-sex chromosomes) in each animal are isogenic or identical. Also included in the invention are animals that are both “autosomally” and “allelically” isogenic whereby each particular pair of chromosomes is internally isogenic or identical within a single animal as well as between animals.

Abstract: The invention features an isolated avian gonadal cell, e.g.

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: 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-11 (GDF-11) 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-11. The animals so treated are characterized by increased muscle tissue.

Abstract: A transgenic animal having a viral expression vector having a nucleic acid which includes (1) a transcriptional start site; (2) a promoter operably linked to the transcriptional start site; and (3) an enhancer operably linked to the promoter, the enhancer comprising the DNA sequence of SEQ ID NO:1 or the RNA equivalent thereof. The vector us useful for making transgenic animals. The transgenic animal may include pig, rat, cow, rabbit, goat, guinea pig, prairie baboon, squirrel, monkey, chimpanzee, bird, frog, toad, chicken, turkey and sheep.

Abstract: The invention relates to a method of expressing proteins in higher eukaryotes in vitro. In general, the invention sets forth a method of expressing exogenous proteins as fusion partners with the immunoglobulin molecules of avian species specifically chickens. The technology involves, in one embodiment, retroviral-mediated gene transfer and transplantation of stem cells from the Bursa of Fabricus in chickens.

Abstract: The present invention provides a microinjection assembly including a microscope, a microinjection system comprising a micromanipulator, a micropipette and a piezo-electric oscillator, and an obliquely angled macro monitoring unit. The present invention also provides methods of microinjecting the germinal disk of an avian egg, thereby delivering a transgenic nucleus, spermatozoon or isolated nucleic acid to the avian embryo. The avian ovum may be returned to a female bird for hard-shell deposit and laying of the egg for hatching as a transfected bird.

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: Disease resistance in domesticated fowl has been associated with the B and Rfp-Y systems of major histocompatability genes. A method for breeding domesticated fowl to produce disease resistant offspring involves selecting at least one parent that has a B genotype, an Rfp-Y genotype or both that is characteristic of disease resistance and mating that parent with a second parent to produce a disease resistant offspring.

Abstract: A composition for in vivo transfection of vertebrate male germ cells comprises a nucleic acid or transgene, and a gene delivery system, and optionally a protective internalizing agent, such as an endosomal lytic agent, a virus or a viral component, which is internalized by cells along with the transgene and which enhances gene transfer through the cytoplasm to the nucleus of the male germ cell. A pharmaceutical preparation and a transfer kit utilize the composition. A method for introducing a polynucleotide into vertebrate male germ cells comprises the administration of the composition to a vertebrate. A method for isolating or selecting transfected cells utilizes a reporter gene, and a method for administering transfected male germ cells utilizes male germ cells which have been transfected in vitro.