Abstract: An embryo that is transferred into the uterus of a recipient female is protected from embryotoxic effects of prostaglandin F2? by exposing the embryo to a prostaglandin antagonist.

Abstract: Provided herein are compositions and methods relating to the involvement of RNF5 in muscle wasting.

Abstract: Compositions and methods are provided for the efficient and reproducible generation of clone animals of all developmental stages. Also provided are methods of use of the same in reproductive and therapeutic cloning protocols.

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: Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. The present invention provides improved mammary expression cassettes useful for the expression of genes at high levels in the milk of transgenic animals. In particular, the present invention provides recombinant signal peptide sequences derived from a-lactalbumin and aS1-casein milk genes suitable for leading protein secretion in the mammary gland.

Abstract: Transgenic and cloned ungulates and particularly cloned cattle are disclosed, wherein such cattle contain a deletion or disruption of the prion gene locus and do not express functional prion protein, and are not susceptible to prion-related diseases such as bovine spongiform encephalopy or Mad Cow Disease.

Abstract: The invention is directed in part to totipotent cells that have one or more artificial chromosomes; processes for producing such cells; processes for using such cells (e.g., nuclear transfer); transgenic embryos and transgenic animals cloned from such cells; and processes for producing such embryos and animals.

Abstract: The invention provides polypeptides, including enzymes, structural proteins and binding proteins, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. Polypeptides, including enzymes and antibodies, and nucleic acids of the invention can be used in industrial, experimental, food and feed processing, nutritional and pharmaceutical applications, e.g., for food and feed supplements, colorants, neutraceuticals, cosmetic and pharmaceutical needs.

Abstract: Methods and compositions for using magnetosomes as cellular contrast agents and markers for magnetic resonance imaging are provided. Certain methods involve synthesizing magnetosomes in a cell as directed by a nucleotide construct comprising an exogenous polynucleotide sequence, wherein the magnetosome serves as a contrast agent or marker for magnetic resonance imaging. Methods of synthesizing and isolating magnetosomes for introduction into immune-matched cells within a tissue or subject for use as a contrast agent or marker for magnetic resonance imaging are also provided. Also provided are methods for stably transfecting cells to express a polypeptide that drives or modulates magnetosome production in the cell, cells produced by such methods and methods for their isolation, transgenic animals comprising at least one eukaryotic cell produced by such methods, and vectors and delivery systems for the transfection of such cells.

Abstract: Improved insemination systems particularly adapted to use for sex-selected sperm sorting include systems which achieve superovulation and then multiple embryo production with sexed embryos. These systems combine with other techniques, including techniques for enhanced sheath fluid and other strategies which minimize stress on the sperm cells, and, potentially, a 2.9 percent sodium citrate sheath solution for bovine species and a hepes bovine gamete media for equine species. Improved collection systems and techniques for the process are described so that commercial application of sperms samples as well as the resulting animals may be achieved.

Abstract: The present invention relates to a method of producing an ungulate having both copies of the IgM heavy chain (mu) rag-1 and/or rag-2 gene eliminated from its genome. Animals which have IgM, rag-1 and/or rag-2 eliminated from their genome are unable to conduct the gene rearrangements that are necessary to generate the antigen receptors of B- or T-lymphocytes, and therefore will not develop native B- or T-cells. Because they are unable to produce B- and T-lymphocytes, these IgM, rag-1, or rag-2 ungulates cannot reject human hematopoietic stem cell preparations, and B- and T-lymphocytes which develop therefrom. Therefore, the present invention also involves injecting into IgM, rag-1, and/or rag-2 deficient ungulates, in utero or shortly after birth, human B- and T-lymphocytes whose immune systems produce human immunoglobulin that can be processed for therapeutic uses in humans.

Abstract: The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. Histological analysis in such knockout mice revealed that bone mineral content, bone mineral density, and bone strength were decreased, and the number of osteoclasts in bone tissues was increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited.

Abstract: The object of this invention is to provide a method for evaluating genetic ability for carcass weight in a bovine individual by using gene markers. According to the method, the nucleotide at the e9 site of the bovine NCAPG gene is determined. When it is G, genetic ability for increasing carcass weight is judged to be higher. Alternatively, the amino acid at the E9 site of the bovine NCAPG gene is determined. When it is methionine, genetic ability for increasing carcass weight is judged to be higher.

Abstract: The invention relates to a non-human transgenic mammal that is useful for the production of a protein of interest that may be toxic to the mammal. The mammal is characterized by the fact that it is transgenic for the production in its milk of an inactive form of the protein of interest, preferably recombinant human insulin. It is not possible to produce recombinant human insulin in transgenic mammals since this molecule has a certain degree of biological activity in the mammals and could be toxic to the mammal. Thus, the invention involves cloning a genetic construct comprising a sequence encoding a modified human insulin precursor under the control of a beta casein promoter in an expression vector. It also involves transfecting the expression plasmid into fetal bovine somatic cells, such as fibroblasts, and enucleating bovine oocytes by nuclear transfer to generate transgenic embryos.

Abstract: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Abstract: Recombinant Factor IX characterized by a high percentage of active protein can be obtained in the milk of transgenic animals that incorporate chimeric DNA molecules according to the present invention. Transgenic animals of the present invention are produced by introducing into developing embryos DNA that encodes Factor IX, such that the foreign DNA is stably incorporated in the DNA of germ line cells of the mature animal. Particularly efficient expression was accomplished using a chimeric construct comprising a mammary gland specific promoter, Factor IX cDNA that lacked the complete or any portion of the 5?-untranslated and 3?-untranslated region, which is substituted with a 5-? and 3?-end of the mouse whey acidic protein gene. In vitro cell cultures of cells explanted from the transgenic mammal of the invention and methods of producing Factor IX from such said culture and methods of treating hemophilia B are also described.

Abstract: The invention provides cloned transgenic ungulates (e.g., bovines) in which prion protein activity is reduced by one or more genetically engineered mutations. Desirably, these transgenic bovines are also genetically modified to express xenogenous (e.g., human) antibodies. Because of their resistance to prion-related diseases such as bovine spongiform encephalopy (also known as mad cow disease), these bovines are a safer source of human antibodies for pharmaceutical uses and a safer source of agricultural products.

Abstract: Methods and means for efficiently downregulating the expression of any gene of interest in eukaryotic cells and organisms are provided. To this end, the invention provides modified antisense and sense RNA molecules, chimeric genes encoding such modified antisense or sense RNA molecules and eukaryotic organisms such as plants, animals or fungi, yeast or molds, comprising the modified antisense and/or sense RNA molecules or the encoding chimeric genes.

Abstract: The invention relates to enzymes having xylanase, mannanase and/or glucanase activity, e.g., catalyzing hydrolysis of internal ?-1,4-xylosidic linkages or endo-?-1,4-ghicanase linkages; and/or degrading a linear polysaccharide beta-1,4-xylan into xylose. Thus, the invention provides methods and processes for breaking down hemicellulose, which is a major component of the cell wall of plants, including methods and processes for hydrolyzing hemicelluloses in any plant or wood or wood product, wood waste, paper pulp, paper product or paper waste or byproduct. In addition, methods of designing new xylanases, mannanases and/or glucanases and methods of use thereof are also provided. The xylanases, mannanases and/or glucanases have increased activity and stability at increased pH and temperature.

Abstract: The present invention relates to cloning technologies. The invention relates in part to immortalized and totipotent cells useful for cloning animals, the embryos produced from these cells using nuclear transfer techniques, animals that arise from these cells and embryos, and materials, methods, and processes for establishing such cells, embryos, and animals.

Abstract: The invention relates to the use of transgenic constructs to produce animal models for the study of chronic wasting disease.

Abstract: Provided herein are transgenic non-human animals having a transgene encoding a variant nicotinic acetylcholine receptor (nAChR) subunit, wherein the variant nAChR subunit is selected from the group consisting of ?6, ?5, and ?2. The transgenic animals display a modified phenotype that includes nicotinic hypersensitivity. Also provided are methods of generating the invention transgenic animals. Further provided are methods for screening a candidate agent for the ability to modulate nicotine-mediated behavior in the invention transgenic animals.

Abstract: The invention provides a transgenic animal producing low-lactose milk, which is transformed with a gene encoding an extracellular lactase-hydrolyzing enzyme cloned from a human small intestinal cDNA library. The invention also provides a new extracellular lactase-phlorizin hydrolase (ecLPH) gene that can express human lactase-hydrolyzing enzyme in the mammary gland of animals. The invention can be used in the production of low-lactose milk.

Abstract: The present invention relates to novel proteins (LITAF and STAT6(B)) and the nucleotide sequences encoding the same. The present invention also relates to the use of the novel peptides and nucleotide sequences of the present invention, or functional fragments thereof, for the regulation of cytokine expression. The present invention also relates to the use of the novel proteins and nucleotides sequences of the present invention for the regulation of inflammatory responses in mammals including the regulation of angiogenesis and tubulogenesis. Also in this regard, the present invention relates to the generation of null mutant animals deficient in the expression of one or both of the proteins of the present invention.

Abstract: The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig? and/or Ig? sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig? and/or Ig? sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig? and/or Ig? results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

Abstract: The present invention relates to the production of a transgenic bovine which comprises a genetic modification that results in inactivation and loss of expression of its endogenous antibodies, and the expression of xenogenous antibodies, preferably human antibodies. This is effected by inactivation of the IgM heavy chain expression and, optionally, by inactivation of the Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of non-bovine antibodies, preferably human antibodies.

Abstract: The invention described herein provides for human antibodies produced in non-human animals that specifically bind to lipopolysaccharide (LPS) from strains Fisher Devlin (International Serogroups) It-2 (011), It-3 (02), It-4 (01), It-5 (010), It-6 (07), PA01 (05), 170003 (02), IATS016 (02/05), and 170006 (02). The invention further provides methods for making the antibodies in a non-human animal, expression of the antibodies in cell lines including hybridomas and recombinant host cell systems. Also provided are kits and pharmaceutical compositions comprising the antibodies and methods of treating or preventing pseudomonas infection by administering to a patient the pharmaceutical compositions described herein.

Abstract: The present invention relates to a method for producing a modified foreign chromosome(s) or a fragment(s) thereof, which comprises the steps of: (a) preparing a microcell comprising a foreign chromosome(s) or a fragment(s) thereof, and transferring said foreign chromosome(s) or a fragment(s) into a cell with high homologous recombination efficiency through its fusion with said microcell; (b) in said cell with high homologous recombination efficiency, inserting a targeting vector by homologous recombination into a desired site of said foreign chromosome(s) or a fragment(s) thereof, and/or a desired site of a chromosome(s) derived from said cell with high homologous recombination efficiency, thereby marking said desired site; and (c) in said cell with high homologous recombination efficiency, causing deletion and/or translocation to occur at the marked site of said foreign chromosome(s) or a fragment(s) thereof.

Abstract: The invention provides novel polypeptides having phospholipase activity, including, e.g., phospholipase A, B, C and D activity, patatin activity, phosphatidic acid phosphatases (PAP)) and/or lipid acyl hydrolase (LAH) activity, nucleic acids encoding them and antibodies that bind to them. Industrial methods, e.g., oil degumming, and products comprising use of these phospholipases are also provided.

Abstract: The present invention relates to treating or ameliorating heart disease associated with poor myocardial performance, e.g., diabetic cardiomyopathy and associated disorders, particularly to treating, preventing or ameliorating such disorders through inhibition of O-GlcNAcylation and/or increased activity of O-GlnNAcase. The invention provides vectors for gene transfer of O-GlnNAcase. In one aspect, the invention provides cells, vectors, formulations comprising them and methods of using them, for the gene transfer of the human O-GlnNAcase gene, e.g., to treat conditions and diseases associated with impaired cardiac contractility, such as that, found associated with diabetic cardiomyopathy. In another aspect, the invention provides non-human transgenic animals and host cells comprising genetically engineered cells having increased activity of O-GlnNAcase.

Abstract: The invention provides non-human transgenic animals, and cell lines, host cells, tissues and isolated organs, comprising the human UDP-glucuronosyltransferase IA (UGT1A) gene locus. In one aspect, the endogenous UGT1A gene locus of the non-human transgenic animal has been partially or completely “knocked out.” In another aspect, the invention is directed to drug screening, design and discovery. In another aspect, the invention is directed to determining the toxicity or metabolism of a compound, e.g., a toxin or drug, including environmental, dietary, cosmetic, biological warfare or other known or potentially toxic compounds. In another aspect, the invention is directed to deteuiining the toxicity or metabolism of a compound during a particular metabolic state of an animal, e.g., including pregnancy, stress, diet, age or a particular genotype.

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: The invention provides cloned transgenic ungulates (e.g., bovines) in which prion protein activity is reduced by one or more genetically engineered mutations. Desirably, these transgenic bovines are also genetically modified to express xenogenous (e.g., human) antibodies. Because of their resistance to prion-related diseases such as bovine spongiform encephalopy (also known as mad cow disease), these bovines are a safer source of human antibodies for pharmaceutical uses and a safer source of agricultural products.

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: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Abstract: The invention features novel methods for the production of large quantities of xenogenous antibodies, such as human antibodies. Preferably, this result is effected by inactivation of IgM heavy chain expression and, optionally, by inactivation of Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of xenogenous antibodies (e.g., non-bovine antibodies), preferably human antibodies.

Abstract: The invention provides inducible expression systems for making short RNA transcripts that can be used in cells and transgenic animals for a variety of applications, including but not limited to, producing and studying the effects of RNAi and microRNA mediated gene silencing.

Abstract: The present invention relates to compositions and methods for inducing mammary epithelial cell differentiation in mammalian subjects. More specifically, the present invention relates to methods for inducing mammary epithelial cell differentiation which comprise increasing the levels of galanin in the mammary tissue of the subject. In one aspect the present invention relates to a method of increasing milk production in a lactating mammal which comprises increasing the level of galanin or an analog thereof in the mammal. In another aspect the present invention relates to a method of enhancing mammary development in a mammal, the method comprising administering to the mammal galanin or an analog thereof in conjunction with prolactin or an analog thereof. In yet another aspect the present invention relates to a method for inhibiting mammary epithelial tumours by administering an inhibitorially effective therapeutic amount of galanin or an analog thereof.

Abstract: The invention describes a concrete schema which allow domesticated ruminant with disease due to Mycobacterium avium subspecies paratuberculosis to serve as an animal model system in order to assess potential systemic and mucosal effects achieved by attempted therapeutic interventions. A key component of this schema is the recognition of the significance of a positive precipitantion band on agar gel immunodiffusion test in terms of the underlying histopathology and subsequent ability to use such data in evaluation necropsy derived data. A second component is the sequential use of newly developed nesting PCR technology and their abilities to identify (and where indicated quantitate) Map DNA present in feces, blood and milk.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of malarial surface protein MSP-1 which is known to be difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred protein candidates for expression using the recombinant techniques of the invention are MSP-1 proteins expressed from DNA coding sequences comprising reduced overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the native MSP-1 gene.

Abstract: A method of reconstituting an animal embryo involves transferring the nucleus from a quiescent donor cell into a suitable recipient cell. The donor cell is quiescent, in that it is caused to exit from the growth and division cycle at G1 and to arrest in the G0 state. Nuclear transfer may take place by cell fusion. The reconstituted embryo may then give rise to one or more animals. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: This invention relates to a method for breeding animals via cloning and the animals obtainable by the method, in particular a method for reproducing animal embryos via efficient nuclear transfer with primordial gametes.

Abstract: The present invention provides animal model systems for cartilage-degenerative disease, which comprise transgenic animals which can express recombinant matrix-degrading enzymes (MDEs), particularly matrix metalloproteinases (MMPs), in a temporally and spatially regulated manner. The invention also provides methods for producing phenotypic indicators of cartilage-degenerative disease in a mammal and methods for determining the potential of a composition to counteract cartilage-degenerative disease. The invention also provides isolated nucleic acids encoding proMMP polypeptides that exhibit constitutive enzymatic activity and isolated proMMP polypeptides.

Abstract: The present invention comprises a system and methods for generating beef. In one embodiment, a method of breeding cattle includes selecting a male bovine having a Wagyu composition, selecting a female bovine having a composition derived from another breed and producing an offspring. In another embodiment, a data system includes a remote station positioned proximate to a cattle area to identify a selected bovine and to receive information, and a central station to exchange information with the remote station. In another embodiment, a method of generating cattle includes identifying a male bovine having a heritable genetic trait derived from the Wagyu breed, identifying a suitable female bovine, and introducing a reproductive material derived from the male bovine into the female bovine. In some embodiments, an omega-3 enriched ration is fed to the cattle during a period prior to slaughter corresponding to the weight of the cattle.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: Compositions useful for inhibiting the growth of bacteria, including bacteria that can cause gastric ulcers, are provided. In addition, transgenic organism that can produce such compositions are provided. Methods of using the compositions to treat or prevent gastric ulcers in a subject, including a human subject, also are provided.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: The present invention relates to the use of the digestive tract of an animal as a bioreactor for the production of a product of interest.