Abstract: A DNA sequence containing a gene encoding a protein, the gene being under the transcriptional control in the DNA sequence of a mammalian milk protein promoter which does not naturally control the transcription of the gene, such DNA sequence including DNA enabling secretion of the protein.

Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Abstract: Non-human transgenic animals overexpressing PDGF-C and cells thereof have been created. The transgenic animals contain a nucleotide sequence that encodes for platelet derived growth factor C (PDGF-C) or an analog thereof, or a functional fragment of PDGF-C or analog thereof. These animals are useful for studying disease states characterized by overexpression of PDGF-C, as well as useful for evaluating therapies intended to treat such diseases.

Abstract: The present invention relates to the stabilization of milk from transgenic animals. In particular, the invention relates to the protection of proteins (e.g. fibrinogen) expressed in milk from transgenic animals by co-expression of a serine proteinase inhibitor (e.g., ?1-antitrypsin) in the milk of the transgenic animals.

Abstract: The present application provides a vector for trapping an unknown gene of Drosophila melanogaster, which is a recombinant plasmid comprising the following nucleotide sequences in this order: an artificial consensus splicing acceptor site; a synthetic “stop/start” sequence; a reporter gene; a drug resistance gene; a gene responsible for a detectable phenotype of the Drosophila melanogaster; and a synthetic splicing donor site. The present application also provide a method for trapping an unknown gene of Drosophila melanogaster by using the vector.

Abstract: A gene-mutated animal such as a mouse which comprises a mutant prsenilin-1 gene comprising a DNA having a sequence encoding a mutant presenilin-1 protein in which an amino acid is substituted with a different amino acid in an amino acid sequence of a presenilin-1 protein; for example, a mutant presenilin protein in which isoleucine at position 213 is substituted with an amino acid other than isoleucine, e.g., threonine, in a mouse presenilin-1 protein. The animal is useful as an animal model which has pathological conditions closer to a human patient with Alzheimer's disease.

Abstract: The present invention relates to mammals into which foreign DNA has been introduced or in which various modifications or substitutions have been made to an integrin ? subunit, thereby generating transgenic or genetically-engineered non-human mammals. In particular, the present invention provides a transgenic mammal in which the endogenous GP IIIa gene has been replaced with an altered or mutant GP IIIa gene in which one or all of the phosphorylable cytoplasmic tyrosine residues have been replaced with non-tyrosine residues such as phenylalanine. Since the platelets in the blood of the resultant transgenic mammals expressing in wild-type mammals, these genetically-engineered animals provide a critical tool for assessing the importance of the phosphorylation reaction for platelet function. The invention is also useful for studying the effect of the mutant GP IIIa integrin subunit on biological processes other than platelet formation.

Abstract: The invention relates to a method for marker-free DNA expression cassette exchange in the genome of cells or parts of cells by using the FLP recombinase mediated cassette exchange. A first DNA expression cassette carrying a positive-negative selection marker flanked by two FLP recombinase recognition target (FRT) sites is integrated into a chromosomal locus of the genome. Following selection of cell clones surviving the conditions for positive selection, the first DNA cassette is exchanged by an incoming second DNA expression cassette located on a circular vector and carrying a transgene flanked by the same FRT sites as the first DNA cassette by using FLP-recombinase. The cell clones surviving the conditions for negative selection contain specifically inserted the gene of the incoming DNA cassette without inserted unwanted vector sequences or positive selectable markers.

Abstract: A transgenic, non-human mammalian animal is capable of expressing a heterologous gene for human or other recombinant physiologically functional fibrinogen holoprotein or individual subunit chain polypeptides thereof or a modified or fusion fibrinogen in mammary glands of the animals and secreting the expressed product into a body fluid. Methodology employing such a mammal yields recombinant physiologically functional fibrinogens, subunit chain polypeptides thereof, and modified or fusion fibrinogens.

Abstract: A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis.

Abstract: The present invention describes a recombinant rodent model for depression. More particularly, the rodent comprises cells expressing mutations in the WFS1 gene. The rodent is preferably a mouse heterologous for mutations in exon 8 of the WFS1 gene. Preferably, the mutations yield a non-functional wolframin protein that lacks all or some of it transmembrane regions. Methods and compositions for making and using the mouse and cells thereof are disclosed.

Abstract: A transgenic zebrafish animal model is disclosed. The model can be used for study of hematopoetic cell differentiation, control, and screening of therapeutic agents and can include a transgenic zebrafish expressing a heterologous Ikaros protein.

Abstract: The present invention relates to nonhuman transgenic animals in which the GP V gene has been modified. The invention is also useful for identifying agents that modulate the biological functions of GP V, including the screening and identification of potential therapeutic agents.

Abstract: The present invention provides methods of identifying anti-HIV compound by contacting human Vpr Interacting Protein (hVIP), or a fragment thereof known to interact with Vpr, with Vpr, or a fragment thereof known to interact with hVIP in the presence of a test compound, and comparing the affinity of the hVIP or fragment thereof to the Vpr or fragment thereof in the presence of the test compound with the affinity of the hVIP or fragment thereof to the Vpr or fragment thereof in the absence of the test compound. The present invention also provides transgenic non-human mammals comprising a recombinant expression vector that comprises a nucleic acid sequence that encodes hVIP.

Abstract: Described herein is a novel gene and its product, WIP, which associates with WASP. The subject invention relates to the isolated WIP gene or cDNA and transgenic mammals that have the WIP gene disrupted in their genome. Also the subject of this invention are methods of treating conditions or diseases in which WIP and/or WASP DNA or protein is deficient and/or defective, for example, mutated or altered, such that an individual is adversely affected. Also described are methods of altering or regulating WIP and its functions in a mammal or in a cell of a mammal, for example in a lymphocyte. A further subject of this invention is an assay to identify drugs which alter the activity of WIP or expression of WIP DNA.

Abstract: Methods and processes for raising the concentration of a first class of immunoglobulin relative to at least a second class of immunoglobulin in a compartment of the body of a non-human animal or the progeny thereof, as well as the animals produced by such methods and processes. Such methods and processes provide for the collection of antibodies produced by mucosal surfaces of the animal. Preferably, the production is in the mammary gland. Antibodies can be collected from the milk of the animal. Antibodies may be used for medical and/or nutritional purposes.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a glucagon receptor gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions. The present invention also relates to diabetes and diabetic condition, as it demonstrates the role of the glucagon receptor in diabetes and diabetic conditions. The present invention further relates to weight gain and weight related conditions, such as obesity, and demonstrates the role of the glucagon receptor in weight gain and weight related conditions, such as obesity.

Abstract: The functional analysis of genes frequently requires the manipulation of large genomic regions. A yeast-bacteria shuttle vector is described, that can be used to clone large regions of DNA by homologous recombination. The important feature of present invention is the presence of the a bacterial replication origin, which allows large DNA insert capacity. The utility of this vector lies in its ability to isolate, manipulate and maintain large fragments in bacteria and yeast, allowing for mutagenesis by yeast genetics and simplified preparation of plasmid DNA in bacteria.

Abstract: The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject.

Abstract: The invention relates to recombinant DNA constructs, a method for producing a recombinant biologically active protein in vivo in the urine of a non-human mammal using a kidney-specific promoter, such as the uromodulin promoter, and the transgenic non-human mammals that serve as urine-based bioreactors for protein production.

Abstract: The present invention provides a method for establishing an expression system of spider dragline silk gene in Bombyx mori. The rate of transformation is about 0.5-1%. In the silk protein produced by the transgenic Bombyx mori obtained by the method of the present invention, the spider dragline silk gene product account for 30% of the total silk proteins.

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

Abstract: A method is provided for repopulating degenerated of immunetolerant mice which lack mature B and T lymphocytes with xenogenic mammalian hepatocytes, particularly primate hepatocytes to generate chimeric mice. In addition, a method of generating a human hepatitis virus-infected chimeric mouse is provided. A preferred xenogenic primate hepatocyte is derived from human, chimpanzee or baboon. These chimeric mice are useful in the investigation of host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis. Methods for monitoring the development of hepatitis and hepatocellular carcinoma as well as methods for testing and screening anti-viral and anti-cancer compounds with this model system are also provided.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in the magnesium-dependent protein phosphatase gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

Abstract: The invention relates to mammalian cell lines and transgenic mammals. More particularly, it relates to a method for producing a rat cell line, a method for producing a transgenic rat, a transgenic rat, a rat cell line, cells and tissue obtained therefrom and uses therefore. The cell line derived from a transgenic mammal comprises: (i) a conditional oncogene, transforming gene or immortalising gene or a cell cycle affecting gene; and (ii) a cell type specific promoter. They include a neuronal cell line in which the cell type specific promoter is an NF-L gene promoter, and a mammary cell line in which the cell type specific promoter is a MMTV gene promoter. The conditional oncogene, transforming gene or immortalising gene is preferably a SV40tsA58 gene.

Abstract: A mammal is provided, in which the LKB1 gene can be deleted phase-specifically and tissue-specifically. These mammals are highly useful as tools to reveal the onset mechanism for diseases caused by LKB1 gene deficiency, such as Peutz-Jeghers syndrome and cancers, as well as to develop therapeutic agents, methods, and so on for the diseases.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a BMP gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a NPY6 receptor gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

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: A knockout transgenic mouse containing a nonfunctional allele of the tumor suppressing gene, annexin VII. This mouse is used as a screening model for potential therapeutic agents useful in the treatment of tumors resulting from an annexin tumor suppressor disease.

Abstract: Methods for preparing cell lines 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 are cell lines for use in the methods, and cell lines and chromosomes produced by the methods. In particular, satellite artificial chromosomes that, except for inserted heterologous DNA, are substantially composed of heteroaromatic are provided. Methods for use of the artificial chromosomes, including for gene therapy, production of gene products and production of transgenic plants and animals are also provided.

Abstract: The present invention provides a transgenic non-human animal whose genome comprises a disruption in its endogenous PDE7A gene, wherein the transgenic animal exhibits decreased expression of functional PDE7A protein relative to wild-type. The present invention further provides a method for creating a transgenic non-human animal exhibiting decreased expression of functional PDE7A protein relative to wild-type. Finally, the present invention provides a method for screening a PDE7A inhibitor for at least one side-effect.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in genes, which are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

Abstract: The present invention provides transgenic non-human animal models of basal cell carcinoma which allows for the characterization of the disease as well as for providing a system for the development and testing of potential treatments.

Abstract: The invention provides non-human, genetically-modified mammals and genetically modified animals cells having a functionally disrupted P2×7 receptor gene. Also provided are methods for producing genetically modified mice in which one or both P2×7R alleles have been functionally inactivated.

Abstract: The present invention discloses a new selective method for inducibly and genetically ablating specific cell lineages in transgenic cell populations, e.g., in transgenic animals. The new method, which permits the production of stable transgenic perigees, and thus can be used at various stages of development of a transgenic cell population, allows both the timing and the degree of cellular ablation to be controlled. As a result the method can be used for a variety of therapeutic applications, as well as to study cell lineages and organogenesis, plus the capacity that residual stem cells have for regeneration.

Abstract: The present invention is directed to animal having functionally disrupted endogenous Tpl2. These animals are resistant to Lps induced endotoxin shock and TNF&agr;-mentioned inflammatory disease. A method of identifying Tpl2 specific inhibitors of endotoxin shock or antagonists to inflammation on and a method of treating or preventing TNF&agr;-mediated inflammatory diseases and Lps induced endotoxin shock in animals are also within the scope of this invention. The present invention is also directed to Tpl2 encoding nucleic acid molecules (SEQ ID NOS: 1 and 3) and polypeptides (SEQ ID NOS: 2 and 4) encoded by such molecules.

Abstract: The present invention relates to a method for detecting an aberrant animal-derived prion gene wherein the method comprises steps of introducing a prion gene of an animal into a mouse to produce a prion gene modified mouse and determining that the prion gene is aberrant when the prion gene modified mouse exhibits heart anomalies; a prion gene modified mouse which exhibits heart anomalies; and a method for detecting drugs which reduce abnormal waves in an electrocardiogram of the mouse.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

Abstract: The present invention provides novel methods for modifying the genome of an animal cell which typically comprise the steps of: constructing a DNA molecule in which desired sequence modifications are contained in a segment of DNA (a “targeting DNA”) that is substantially isogenic with a DNA in the cell genome (a “target DNA”); introducing the targeting DNA construct into the cell (e.g., by microinjection, electroporation, transfection, or calcium phosphate precipitation); and selecting cells in which the desired sequence modifications have been introduced into the genome via homologous recombination.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a ubiquitin-specific protease 16 gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

Abstract: Cells and non-human transgenic animals have been engineered to be deficient in the gene encoding the melcanocortin-3 receptor protein (MC-3R). MC-3R deficient transgenic animals have increased fatmass and reduced lean body mass, showing that the MC-3R protein is involved in the regulation of body fat and muscle mass. These MC-3R deficient transgenic animals can be used to select for and test potential modulators of MC-3R. This data allows for methods of screening for MC-3R modulators which effect body weight and associated methods of treating various disorders associated with inappropriate regulation of body weight. The disclosure also relates to a MC-3R/MC-4R double knockout mouse which can be used to select for and test potential modulators (e.g., agonists or antagonists) of MC-3R and/or MC-4R. It is shown that MC-3R serves a non-redundant role, when compared to MC-4R, in the regulation of energy homeostasis.

Abstract: A chimeric, non-human animal can be produced by a method that entails providing a microcell that contains one or more foreign chromosomes or fragment(s) thereof and then fusing the microcell with a pluripotent cell, thereby introducing the foreign chromosome(s) or fragment(s) into the latter. The pluripotent cell thus obtained can be used to generate a chimeric, non-human animal, the cells, tissues, and/or progeny of which can be the source of a product, such as an antibody, that is associated with one or more genes on the foreign chromosome(s) or fragment(s).

Abstract: The present invention relates to the synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitivity sites of the &bgr;-globin locus are sufficient to result in high level expression of human &agr;- or &bgr;-globin transgenes.

Abstract: The invention provides nucleic acid sequences which regulate expression of a nucleotide sequence of interest. In particular, the invention provides nucleic acid sequences which regulate expression of a nucleotide sequence of interest in an age-related manner and/or in a liver-specific manner. The invention further provides methods of using the regulatory nucleic acid sequences provided herein for age-related and/or liver-specific expression of nucleotides sequences of interest. The invention also provides host cells and transgenic non-human animals which harbor the regulatory nucleic acid sequences of the invention. The compositions and methods of the invention are useful in regulating expression of a nucleotide sequence of interest in an age-related and/or liver-specific manner.

Abstract: Described is a genetically modified non-human animal model for studying the peripheral and central pathways of energy homeostasis. Also disclosed are methods of identifying compounds for regulating such pathways and a Pomc mutant mouse.

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: Transgenic organisms (in particular, transgenic animals or plants) bearing positive and/or negative selectable markers are described along with their use in various methods including tissue/cell culture techniques, methods of making monoclonal antibodies, methods of selectively eliminating or depleting a particular tissue/cell type, methods of screening compounds for pharmacological activity and methods of determining the effect of a deficit in a first class of cells or the characteristics of a second class of cells in an organism.

Abstract: The invention provides transgenic nonhuman mammals producing phosphorylated lysosomal proteins in their milk, and methods of generating the same. Phosphorylation occurs at the 6′ position of a mannose side chain residue. Also provided are methods of purifying lysosomal proteins from milk, and incorporating the proteins into pharmaceutical compositions for use in enzyme replacement therapy.