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 present invention provides a porcine beta-casein gene, a porcine beta-casein gene promoter, an expression vector comprising the same promoter, and a method for the production of a target protein using the same expression vector. The promoter of the present invention facilitates mammary gland-specific expression of the target protein and therefore can be useful for high-concentration production of beneficial proteins in milk.

Abstract: The invention provides compositions and methods for producing androstenedione (4-androstenedione), of improved purity and for modulating its production, for example by deletion or inactivation of ksdA, cxgA, cxgB, cxgC, or cxgD. The invention also provides methods and compositions, including nucleic acids that encode enzymes, for producing 1,4-androstadiene-3,17-dione (ADD) and related pathway compounds, including 20-(hydroxymethyl)pregna-4-en-3-one and 20-(hydroxymethyl)pregna-1,4-dien-3-one. The compositions of the invention include nucleic acids, probes, vectors, cells, transgenic plants and seeds, transgenic animals, kits and arrays.

Abstract: The present invention relates to a transgenic animal, which comprises in its genome a recombinant polynucleotide encoding one or more reporter proteins and a monocyte chemotactic protein-1 (MCP-1) promoter, wherein the one or more reporter proteins are expressed under the control of the MCP-1 promoter. A method for monitoring endogenous expression of MCP-1 in vivo is also provided, which is useful for identifying a regulator of the expression of MCP-1 or an anti-inflammatory agent.

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: 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 a process of expressing secreted recombinant human alpha-fetoprotein (rHuAFP) in the milk or urine of transgenic mammals.

Abstract: The invention provides methods for managing livestock for breeding or production based on one or more measurements of mitochondrial function. Measurement of mitochondrial function may also be correlated with a calculated or known feed efficiency of livestock animals to yield a predicted feed efficiency for the animal. The invention overcomes deficiencies associated with phenotypic assays for predicted breeding and production value.

Abstract: A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.

Abstract: The invention relates to mammalian PAI-I ligands and modulators. In particular, the invention relates to polypeptides, polypeptide compositions and polynucleotides that encode polypeptides that are ligands and/or modulators of PAI-I. The invention also relates to polyligands that are homopolyligands or heteropolyligands that modulate PAI-I activity. The invention also relates to ligands and polyligands localized to a region of a cell. The invention also relates to localization tethers and promoter sequences that can be used to provide spatial control of the PAI-I ligands and polyligands. The invention also relates to inducible gene switches that can be used to provide temporal control of the PAI-I ligands and polyligands. The invention also relates to methods of treating or preventing atherosclerosis. The invention also relates to methods of treating or preventing fibrosis.

Abstract: The invention concerns the reconstruction in vitro of non-human mammal embryos by a method which consists in treating the nucleus of a somatic donor cell prior to its transfer into a receiver cytoplasm, said treatment comprising controlled proteolysis of non-histone proteins, and inducing an isomorphic swelling of said nucleus.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding immunodeficiency proteins. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding immunodeficiency proteins.

Abstract: The present invention is directed to a Trypanosome-resistant, non-human transgenic animal whose somatic and germ cells comprise a nucleic acid which encodes an apolipoprotein L-I polypeptide (apoL-I). The apoL-I protein has the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. The first nucleic acid transgene is operatively associated with at least one expression regulatory sequence. Methods of producing and raising such transgenic animals as well as transgenic eggs and sperm are also disclosed.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with neurodevelopmental disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with a secretase disorder. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides a genetically modified bovine or cell comprising at least one edited chromosomal sequence. In particular, the chromosomal sequence is edited using a zinc finger nuclease-mediated editing process. The disclosure also provides zinc finger nucleases that target specific chromosomal sequences in the bovine genome.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal involved in cardiovascular disease. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequences involved in cardiovascular disease and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with AD. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study AD development and methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with AD.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with cognitive disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences associated with cognitive disorders.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with ASD. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study ASD development and screen agents for assessing their effect on progression or symptoms of an ASD.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with cognitive disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding ABC transporter proteins. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding ABC transporter proteins.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with Parkinson's disease. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study PD development and screen agents for assessing their effect on progression or symptoms of PD.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence involved in tumor suppression and the nucleic acids encoding the zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with addiction disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence encoding addiction-related proteins and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for addiction and withdrawal side effects and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences associated with schizophrenia. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence associated with schizophrenia and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences associated with schizophrenia.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with nociception or taste disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding inflammation-related proteins. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding inflammation-related proteins.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with neurotransmission disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

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-glucanase 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 provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with trinucleotide repeat expansion disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: A non-human transgenic mammalian animal, as described above, contains one or more exogenous double stranded DNA sequence(s) stably integrated into the genome of the animal, which comprises trans-acting regulatory units controlling expression of DNA sequences encoding proteins to be secreted into the milk of transgenic mammals. The DNA sequence of the trans-regulatory gene encodes transcriptional activating proteins, which are not secreted but made in a temporally controlled and mammary tissue specific manner. The DNA sequence containing the protein to be secreted in the milk is constructed on a separate gene sequence under the regulation of a minimal promoter and a trans-activation binding domain. The transgenic mammals are preferably pigs, cows, sheep, goats and rabbits. A related composition and method for making transgenic proteins which require specialized propeptides for proper post-translational processing is also described.

Abstract: This application is in the field of sialic acid chemistry, metabolism, antigenicity, and the production of transgenic non-human mammals with altered sialic acid production. More particularly, this application relates to N-glycolylneuraminic acid (Neu5Gc) being an immunogen in humans, and the production of Neu5Gc-free mammalian products for laboratory and human use.

Abstract: The invention relates to the production of proteins and other substances of interest in saliva of transgenic animals, particularly in mammals that produce large quantities of saliva, particularly monogastric ruminants, and ovine, caprine and bovine mammals. Preferred embodiments of the invention relate in particular to the production of foreign and modified proteins in the transgenic saliva of these animals, including particularly human fibrinogen, human prothrombin and human thrombin, among others. The invention relates as well to methods, devices, genetic constructs and to transgenic constructs for making the proteins and other substances of interest, to novel saliva and saliva-derived compositions, novel products produced from the saliva, and to uses of the saliva, saliva-derived compositions and novel products.

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 invention relates to a method of producing a protein of interest, comprising making a non-human transgenic mammal that produces said protein in its milk, obtaining said milk from the non-human transgenic mammal and purifying said protein of interest from the milk. Transgenic bovine animals were generated, which are able to produce human growth hormone in mammary glands. The method involves cloning of a genetic construct encoding hGH gene and beta casein promoter conveniently in an expression vector. It also includes transfection procedures into fetal bovine somatic cells, generally fibroblasts, and the nuclear transfer into enucleated bovine oocytes, generating thus transgenic embryos.

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: 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 relates to antibodies and subsequences thereof that specifically bind to poxvirus B5R envelope protein, antibodies and subsequences thereof that specifically bind to pox virus H3L envelope protein, and combinations thereof.

Abstract: A prognostic marker for breast cancer and a composition for inducing obesity are provided, wherein said marker and said composition comprise HCCR-1.

Abstract: The present invention provides a mammary gland-specific human erythropoietin expression (hEPO) vector, transgenic animal and method for producing human erythropoietin using the same. The inventive hEPO-expressing transgenic animals express a mammary gland-specific EPO at an extremely higher concentration than the convention method. The hEPO produced from inventive transgenic animals shows better stability and superior physiological activity than those of the same kind of commerally available protein. Therefore, the inventive hEPO-expressing transgenic animals can be effectively used for production of EPO showing a superior physiological activity than the existing EPO.

Abstract: The present invention concerns methods and means to produce humanized antibodies from transgenic non-human animals. The invention specifically relates to novel immunoglobulin heavy and light chain constructs, recombination and transgenic vectors useful in making transgenic non-human animals expressing humanized antibodies, transgenic animals, and humanized immunoglobulin preparations.

Abstract: The invention relates to the production of proteins and other substances of interest in saliva of transgenic animals, particularly in mammals that produce large quantities of saliva, particularly monogastric ruminants, and ovine, caprine and bovine mammals. Preferred embodiments of the invention relate in particular to the production of foreign and modified proteins in the transgenic saliva of these animals, including particularly human fibrinogen, human prothrombin and human thrombin, among others. The invention relates as well to methods, devices, genetic constructs and to transgenic constructs for making the proteins and other substances of interest, to novel saliva and saliva-derived compositions, novel products from the saliva, and to uses of the saliva, saliva-derived compositions and novel products.

Abstract: The present invention relates to fusion proteins comprising a microorganism targeting molecule (e.g., immunoglobulin) and a biocide. The present invention also relates to therapeutic and prophylactic methods of using a fusion protein comprising a microorganism targeting molecule and a biocide in diverse fields.

Abstract: The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-modulated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

Abstract: This invention relates to phytases, polynucleotides encoding them, uses of the polynucleotides and polypeptides of the invention, as well as the production and isolation of such polynucleotides and polypeptides. In particular, the invention provides polypeptides having phytase activity under high temperature conditions, and phytases that retain activity after exposure to high temperatures. The phytases of the invention can be thermotolerant and/or thermostable at low temperatures, in addition to higher temperatures. The phytases of the invention can be used in foodstuffs to improve the feeding value of phytate rich ingredients. The phytases of the invention can be formulated as foods or feeds or supplements for either to, e.g., aid in the digestion of phytate. The foods or feeds of the invention can be in the form of pellets, liquids, powders and the like.

Abstract: The invention provides a new type of a capsid protein VP1 of human enterovirus 71, named as MEL701-VP1 and functional/structural variants thereof, which is used for protection against enterovirus. The transgenic animal producing the protein, the composition comprising the protein and the method for production thereof are also provided.

Abstract: The invention relates to a gene (cDNA) encoding a bovine myostatin protein. The nucleic acid coding sequence is identified as SEQ ID NO:1 and the protein sequence is identified as SEQ ID NO:2. A mutant gene (SEQ ID NO:3) in which the coding sequence lacks an 11-base pair consecutive sequence (SEQ ID NO:11) of the sequence encoding bovine protein having myostatin has been sequenced. It has been shown that cattle of the Belgian Blue breed homozygous for the mutant gene lacking myostatin activity are double-muscled. A method for determining the presence of muscular hyperplasia in a mammal is described. The method includes obtaining a sample of material containing DNA from the mammal and ascertaining whether a sequence of the DNA encoding (a) a protein having the biological activity of myostatin, is present and whether a sequence of the DNA encoding (b) an allelic protein lacking the activity of (a), is present.

Abstract: The instant invention relates to a transgenic, non-human animal that carries a mutation in the gene encoding C-reactive protein (CRP). Preferably, the invention relates to an animal comprising a homozygous CRP-deficient mouse and techniques for producing such animals. The invention also relates to organs, tissues, cells, cell lines and sub-cellular fractions derived from such animals. Techniques for generating total or tissue-specific CRP knockout animals are also described. The invention further relates to the use of such knockout animals for the study of the role of CRP proteins in vivo or ex vivo, particularly in relation to its role in inflammatory pathway and in the etiology human diseases.

Abstract: Materials and methods for producing fibrinogen in transgenic non-human mammals are disclosed. DNA segments encoding A?, B? and ? chains of fibrinogen are introduced into the germ line of a non-human mammal, and the mammal or its female progeny produces milk containing fibrinogen expressed from the introduced DNA segments. Non-human mammalian embryos and transgenic non-human mammals carrying DNA segments encoding heterologous fibrinogen polypeptide chains are also disclosed.