Abstract: The present invention provides novel methods for improving the efficiency of artificial activation of unfertilized mammalian oocytes by reducing the intracellular concentration of Zn2+ in the oocyte. The methods of the invention may additionally comprise a preceding step of increasing the intracellular concentration of Ca2+ in the oocyte prior to reduction of the intracellular Zn2+ concentration. The invention further provides unfertilized oocytes activated by the disclosed methods and viable mammalian animals produced from unfertilized oocytes activated by the disclosed methods.

Abstract: Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with red fluorescent protein in the loxp cassette, dominant black (?G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which the HTNCre was applied.

Abstract: A genetically modified livestock animal, and methods of making and using the same, the animal comprising a genetic modification to disrupt a target gene selectively involved in gametogenesis, wherein the disruption of the target gene prevents formation of functional gametes of the animal. Animals that create progeny with donor genetics, and methods of making and using the same. Cells, and methods of making and using the cells, with a genetic modification to disrupt a target gene selectively involved in gametogenesis.

Abstract: The present invention relates to the proline rich transmembrane protein 2 (PRRT2) gene, and the identification of mutations and variations in PRRT2 that give rise to seizure and movement disorders. Accordingly, the present invention provides methods for the diagnosis or prognosis of such disorders by identifying alterations in the PRRT2 gene. Identification of alterations in the PRRT2 gene also enables the identification of subjects with an increased likelihood of having an offspring predisposed to such disorders. The present invention also provides an isolated nucleic acid molecule comprising an alteration in the PRRT2 gene, wherein said alteration produces a seizure and/or movement disorder phenotype. Also provided is an isolated PRRT2 polypeptide that comprises an alteration which produces a seizure and/or movement disorder phenotype.

Abstract: Methods of using hypermethylated transposons to create genetically modified animals that express interfering RNAs are described.

Abstract: A genetically modified livestock animal comprising a genome that comprises inactivation of a neuroendocrine gene selective for sexual maturation, with the inactivation of the gene preventing the animal from becoming sexually mature. Methods of using, and processes of making, the animals are taught.

Abstract: The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

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: This invention relates to polypeptides having aldolase activity, including pyruvate activity such as, without limitation, HMG and/or KHG aldolase activity, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. In some embodiments, the invention is directed to polypeptides having aldolase activity, including pyruvate activity such as, without limitation, HMG and/or KHG aldolase activity, including thermostable and thermotolerant activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The polypeptides in accordance with the invention can be used in a variety of pharmaceutical, agricultural and industrial contexts.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with, red fluorescent protein in the loxp cassette, dominant black (?G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which it was applied.

Abstract: The present invention relates to the field of biotechnology or genetic engineering. More specifically, the present invention relates to a multiple inducible gene regulation system that functions within cells to simultaneously control the quantitative expression of multiple genes.

Abstract: The instant invention relates to the use of 24-hydroxylated vitamin D compounds as therapeutics in mammalian bone fracture repair. In addition, the instant invention relates to novel 24-hydroxylated vitamin D compound receptors which can be employed in the development of compounds capable of facilitating fracture repair in animals. The instant invention also relates to nucleic acids encoding such receptors as well as vectors, host cells, transgenic animals comprising such nucleic acids and screening assays employing such receptors.

Abstract: In some aspects, the invention provides compositions and methods for inhibiting viral infection. In some aspects, the invention provides compositions and methods useful for identifying antiviral compounds.

Abstract: Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with, red fluorescent protein in the loxp cassette, dominant black (?G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which it was applied.

Abstract: Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with red fluorescent protein in the loxp cassette, dominant black (?G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which the HTNCre was applied.

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

Abstract: The application is in the field of transgenic (non-human) organisms, sialic acid chemistry, metabolism and antigenicity. More particularly, the invention is related to a method to produce Neu5Gc-free animals and products therefrom comprising disrupting the CMAH gene and thereby reducing or eliminating Neu5Gc from biological material of non-humans.

Abstract: The present relates to use of follistatin-like related gene (FLRG) to increase muscle mass in a subject. As such, methods of ameliorating the severity of a pathologic condition characterized, at least in part, by a decreased amount, development or metabolic activity of muscle are provided. In addition transgenic non-human mammals expressing FLRG and having increased muscle mass as compared to a corresponding mammal having a myostatin-null mutation or a decreased level of myostatin are provided.

Abstract: An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes are alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

Abstract: The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter; and (b) a DNA sequence which encodes a receptor for advanced glycation endproducts (RAGE), wherein the promoter and the DNA sequence which encodes the receptor for advanced glycation endproducts (RAGE) are operatively linked to each other and integrated in the genome of the non-human animal, and wherein said non-human animal exhibits a reduced amount of cerebral tissue infarcted following a transient middle cerebral artery occlusion compared to an identical non-human animal lacking said DNA sequence.

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

Abstract: Compositions and methods for use of TALENs to make genetically modified livestock are set forth. The methods may include reporters for selecting cells or embryos that have been modified by TALENs for use as progenitor cells to make founder animals.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/invertebrate retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in ADME and toxicology. 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 ADME and toxicology 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 involved in ADME and toxicology.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with MD. 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 MD development and methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with MD.

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 invention further provides phytases which have increased gastric lability. 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.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding cytochrome P450 (CYP) proteins. 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 CYP proteins, as well as methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: Particular aspects show that the signal peptide remains intact on the mature CD18 molecule on ruminant leukocytes rendering these cells susceptible to cytolysis by Lkt. Comparative amino acid sequence analysis of the signal peptide of CD18 of eight ruminants and five non-ruminants revealed that the ruminant CD18 signal peptides contain ‘cleavage-inhibiting’ glutamine (Q), compared to ‘cleavage-conducive’ glycine in non-ruminants, at position ?5 relative to the cleavage site. Mutagenesis of Q at position ?5 of the bovine CD18 signal peptide to G resulted in the abrogation of Lkt-mediated cytolysis of transfectants expressing bovine CD18 carrying the Q(?5)G mutation. Provided is novel technology to clone cattle and other ruminants expressing CD18 without the signal peptide on their leukocytes, providing ruminants that are less susceptible to M. haemolytica. Methods for treating conditions and/or diseases associated with M. haemolytica (e.g.

Abstract: The present invention provides a method for diagnosing and detecting diseases associated with colon. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in colon diseases (CCAT) and antibodies binds to CCAT. The present invention provides that CCAT is used as targets for screening agents that modulates the CCAT activities. Further the present invention provides methods for treating diseases associated with colon.

Abstract: The invention provides, among other things, activatable prothrombin, compositions comprising prothrombin, transgenic organisms for making prothrombin, methods for making the transgenic organisms, methods for making prothrombin-comprising compositions and for further purifying prothrombin from the compositions. Illustrative embodiments of the invention particularly provide transgenic mammals that express an exogenous gene for prothrombin and excrete the prothrombin encoded by the gene into their milk. In a highly particular illustrative embodiment in this regard the invention provides transgenic female pigs that express prothrombin in their milk. In this regard, the invention relates particularly to female pigs having stably incorporated in their genomes a DNA comprising a region that encodes prothrombin operably linked to a mammary gland-specific promoter. Further in this regard the invention relates to the milk containing the prothrombin and to prothrombin-containing compositions derived from the milk.

Abstract: The present invention relates to a porcine alpha-S1-casein gene, a porcine alpha-S1-casein gene promoter, an expression 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 the mammary gland-specific expression of the target protein. Accordingly, an animal transformed with the promoter secretes the target protein in milk at high concentration, and thus can be advantageously used for the production of useful proteins.

Abstract: The present invention provides isolated polynucleotides encoding promyostatin polypeptides or a peptide portion thereof, polynucleotides complementary thereto, and oligonucleotides that can specifically hybridize to such polynucleotides. The present invention also provides an isolated polynucleotide encoding a mature myostatin peptide.

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

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 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 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 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 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: 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.