Abstract: Disclosed is a method for constructing a nucleus-implanted egg, a parthenogenetic embryo and for producing a parthenogenetic mammal each having 2 haploid genome sets originating in mammalian ova, and provides methods of constructing a nucleus-implanted egg having a haploid genome set derived from primitive ovarian follicle egg (ng ovum) and a haploid genome set from MII phase (second meiosis metaphase) egg (fg ovum), a parthenogenetic embryo and a parthenogenetic mammal, including steps (1) introducing ng ovum into a nucleus-deleted deleted germinal vesicle stage (GV) egg, developing the obtained egg to MII phase by in vitro maturing and culturing to prepare a first nucleus-implanted egg, and (2) extracting MII phase chromosome from the first nucleus-implanted egg and introducing it into other fg ovum to prepare a second nucleus-implanted egg, wherein a ng or fg ovum from which an imprinted gene undergoing epigenetic modification during sperm generation is used.

Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.

Abstract: The invention generally relates to polyunsaturated fatty acid (PUFA) polyketide synthase (PKS) systems isolated from or derived from non-bacterial organisms, to homologues thereof, to isolated nucleic acid molecules and recombinant nucleic acid molecules encoding biologically active domains of such a PUFA PKS system, to genetically modified organisms comprising PUFA PKS systems, to methods of making and using such systems for the production of bioactive molecules of interest, and to novel methods for identifying new bacterial and non-bacterial microorganisms having such a PUFA PKS system.

Abstract: The invention provides a non-human transgenic animal as a model of type 2 diabetes manifesting a symptom of type 2 diabetes by excessive expression of the active SREBP-2 protein in pancreatic ?-cells by introducing a recombinant DNA in which a DNA encoding the active SREBP-2 protein is disposed under the control of a promoter, and a method for screening therapeutic agents of diabetes using the transgenic animal.

Abstract: The invention relates to transgenic avians whose genome contains nucleotide sequences which encode therapeutic polynucleotides that correspond to one or more certain sequences in the genome of an avian pathogen.

Abstract: Mechanisms regulating cell proliferation stop and differentiation initiation during the development stage of mammalian embryo, and the proteins involved therein, are presented. Differentiation regulators, methods of regulating differentiation, transgenic organisms with loss of expression of the differentiation regulator, and methods of preparing the transgenic organisms, are provided.

Abstract: Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Abstract: A transgenic animal having diabetes, which is more suitable as a model of human than rodents, and its preparation method are disclosed. The method for preparing the transgenic pig comprises introducing a nucleic acid into a fertilized egg, clonal egg or embryo, the nucleic acid comprising a foreign gene which contains a region encoding dimerization domain of hepatocyte nuclear factor-1?, but does not encode a normal hepatocyte nuclear factor-1?, and a promoter located upstream of the foreign gene, which promoter is capable of expressing the foreign gene in a pig cell; and developing an individual from the fertilized egg, clonal egg or embryo.

Abstract: The present invention relates to provide a non-human animal model unresponsive to a synthetic compound wherein a gene function encoding TLR7 that recognizes an immunopotentiating synthetic compound such as imidazoquinoline lacks on is genomic locus. Whole or part of a gene fragment of a gene site including an intracellular region and a transmembrane region of a TLR7 gene obtained from a mouse gene library is replaced by a plasmid including poly A signal and a marker gene to construct a targeting vector. Then, this targeting vector is linearized and transferred into embryonic stem cells. The target embryonic stem cells wherein the TLR7 gene function is deleted are microinjected into a mouse blastocyst to generate a chimeric mouse. Then, this chimeric mouse is crossed with a wild-type mouse to generate a heterozygote mouse. Next, the heterozygote mice are intercrossed to obtain a TLR7 knockout mouse.

Abstract: The invention provides a method of making a pluripotent stem cell from a cell that is not pluripotent, such as from a differentiated stem cell or a lineage-restricted stem cell. The methods comprise culturing the starting cell in the presence of one or more epigenetic altering agents, such as a histone deacetylase inhibitor and/or a DNA methyltransferase inhibitor. Pluripotent stem cells are also provided, as are methods of treating or preventing a disease, disorder, or condition in a mammal using the cells.

Abstract: An object of the invention is to effectively prepare a fish embryo with a correct chromosomal ploidy by nuclear transplantation in which an exogenous fish nucleus is transplanted in a cytoplasmic recipient. For this object, the invention comprises a step of preparing a fish embryo by transplanting a fish cell nucleus to an unfertilized egg. The step of preparing a fish embryo comprises a step of imposing physical and/or chemical stress to the unfertilized egg after activation. By imposing such stress, the stage of haplosis in a female nucleus which happens at the early stage of a series of developmental steps occurring in an unfertilized egg is suppressed and the correct ploidy of an obtained embryo is at least secured.

Abstract: A non-human animal that produces human tissue factor (TF) without substantially producing non-human animal tissue factor, said animal having a genome in which cDNA encoding human TF has been inserted upstream of the translation initiation codon for the non-human animal genomic TF gene.

Abstract: The present invention relates, in general, to development of non-human transgenic animals expressing a human blood clotting factor, such as Factor VIII, Factor VII, Factor IX and von Willebrand factor. The invention further provides methods of detecting immunogenic events against human blood clotting factor using the transgenic animals described.

Abstract: The present invention provides new lentiviral vectors that include an anti-repressor element (ARE) and, optionally, a scaffold attachment region (SAR). The lentiviral vectors provide expression of a heterologous nucleic acid in at least 50% of the cells of multiple cell types when used for lentiviral transgenesis. In certain embodiments of the invention the heterologous nucleic acid encodes an RNAi agent such as an shRNA. The invention further provides transgenic nonhuman animals generated using a lentiviral vector that includes an ARE and optional SAR. In addition, the invention provides a variety of methods for using the vectors including for achieving gene silencing in eukaryotic cells and transgenic animals, and methods of treating disease. The invention also provides animal models of human disease in which one or more genes is functionally silenced using a lentiviral vector of the invention.

Abstract: A combination comprising two or more polynucleotides that are differentially expressed in fat animals compared to lean animals or two or more proteins produced by the expression of such polynucleotides is disclosed. The combination and probes based upon the combination are used for formulating a prognosis that an animal is likely to become fat, developing a diagnosis that an animal is fat, screening substances to determine if they are useful for modulating the amount of adipose tissue on an animal, and detecting the differential expression of one or more genes differentially expressed in fat animals compared to lean animals in a sample. Methods for using class predictor gene profiles to identify fat and lean animals are also disclosed.

Abstract: The present invention relates to vectors, compositions and methods for conditional, Cre-lox regulated, RNA interference. The vectors allow for spatial and temporal control of miRNA expression in vivo.

Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.

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: Disclosed are methods, compositions, and systems for transforming silkworms to produce spider silk and analogs of spider silk. In certain embodiments, the method may include inserting a DNA sequence coding for at least a portion of a spider silk fibroin polypeptide, or an analog of a spider silk fibroin polypeptide, positioned between at least a portion of the 5? and 3? ends of a silkworm fibroin gene to generate a fusion gene construct having a sequence that encodes for a polypeptide comprising both spider silk fibroin and silkworm silk fibroin sequences. In certain embodiments, the fused gene is able to replace a native gene present in the silkworm such that the transformed silkworm expresses a polypeptide comprising a spider silk fibroin polypeptide, or an analog thereof, and expresses significantly less of the native silkworm silk.

Abstract: The invention relates to genetically manipulated animals that are deficient in the expression of Casapse-9, a protein involved in programmed cell death. The invention further relates to methods for preventing specific types of cell death associated with Caspase-9 activation.

Abstract: The present invention relates to vectors, compositions and methods for conditional, Cre-lox regulated, RNA interference. The vectors allow for spatial and temporal control of miRNA expression in vivo.

Abstract: The invention includes avians containing an artificial chromosome in their genome and methods of making the avians.

Abstract: The present invention relates to the use of regulatory sequences for mediating specific, early transient expression in proliferative neuronal determined cells. Furthermore, the uses of recombinant nucleic acid molecules comprising said defined regulatory sequences for mediating specific, early transient expression in proliferative neuronal determined cells as well as for the generation of non-human transgenic organisms and/or host cells are disclosed. In addition, the invention provides for transgenic non-human animals and/or host cells comprising said regulatory sequences and/or recombinant nucleic acid molecules. The invention also describes methods for the preparation of such vectors, host cells and transgenic non-human animals as well as methods for the detection and/or isolation of neuronal determined cells.

Abstract: The present invention has for its object to provide a transgenic bird with a foreign gene containing a feline-derived protein-encoding sequence as transferred therein, and a method of producing the same. The present invention provides a method of producing a feline-derived protein by using a transgenic bird with a method which comprises infecting an avian embryo with a replication defective retrovirus vector containing a foreign gene by microinjection thereof into the early heart or blood vessel formed in the embryo and allowing the embryo to hatch.

Abstract: The present invention refers to a method for the transfer of DNA sequences or exogenous genes into animal sperm cells by means of the use of episomal vectors. The invention also relates to the use of “Sperm Mediated Gene Transfer” (SMGT) technology for the creation of genetically modified individuals.

Abstract: The present invention provides a method for producing systemic red fluorescent zebrafish. The present invention also provides a new gene fragment and a systemic red fluorescent zebrafish.

Abstract: The present invention is directed to the use of the maize Ac/Ds transposable elements in vertebrates.

Abstract: Isolated nucleic acids comprising a lipocalin gene promoter region, isolated nucleic acids comprising a human lipocalin gene, isolated nucleic acids encoding a lipocalin polypeptide, isolated lipocalin polypeptides, and uses thereof. The disclosed lipocalin nucleic acids and polypeptides can be used to generate a mouse model of male infertility, for drug discovery screens, and for therapeutic treatment of fertility-related conditions.

Abstract: A new type of gene trap cassette, which can induce conditional mutations, relies on directional site-specific recombination systems, which can repair and re-induce gene trap mutations when activated in succession. After the gene trap cassettes are inserted into the genome of the target organism, mutations can be activated at a particular time and place in somatic cells. The gene trap cassettes also create multipurpose alleles amendable to a wide range of post-insertional modifications. Such gene trap cassettes can be used to mutationally inactivate all cellular genes temporally and/or spatially. Cells which contain the inventive gene trap cassette can be used for identification and/or isolation of genes and for the creation of transgenic organisms to study gene function at various developmental stages, including the adult, as well as for the creation of animal models of human disease useful for in vivo drug target validation.

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: 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: An animal model of coronary heart disease has been developed where myocardial infarct can be induced by altering the animal's diet. In all embodiments, this animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and apolipoprotein E (ApoE). In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SR-BI?/?) and an impaired ApoE expressor (hypoE). The impaired ApoE gene results in only 2-5% expression of ApoE and a reduction in cholesterol homeostasis. Resulting animals are predisposed to hypercholesterolemia but can live longer than a year on a normal low fat diet. Serum plasma levels can be significantly elevated by changing the animal's diet to one containing high levels of fat and cholesterol. Within a month on a high fat, high cholesterol diet, animals develop atherosclerosis and myocardial infarction occurs.

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

Abstract: The novel germ-line transformation systems disclosed in this patent application allow the physical deletion of transposon DNA following the transformation process, and the targeting of transgene integrations into predefined target sites. In this way, transposase-mediated mobilization of genes-of-interest is excluded mechanistically and random genomic integrations eliminated. In contrast to conventional germ-line transformation technology, our systems provide enhanced stability to the transgene insertion. Furthermore, DNA sequences required for the transgene modification (e.g. transformation marker genes, transposase or recombinase target sites), are largely removed from the genome after the final transgene insertion, thereby eliminating the possibility for instability generated by these processes.

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 features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection. The animals of the invention are also useful in assessing toxicity of various agents, as well as the activity of agents in decreasing blood lipids.

Abstract: Transgenic, non-human animal model of cancer, methods of making such animals and methods of using such animals to screen test compounds are provided.

Abstract: A transgenic non-human animal with alterations in the MBL gene is prepared by introduction of a gene encoding an altered MBL protein into a host non-human animal. Methods for using transgenic mice so generated to screen for agents that effect MBL's cellular modulating activity are also provided.

Abstract: The present invention relates to the treatment of CJD and other spongiform encephalopathies by increasing the level and/or activity of hydrogen peroxide degrading enzymes, such as catalase and glutathione peroxidase, in order to deplete hydrogen peroxide and prevent the build up of gaseous oxygen in the brains of patients. Various aspects are provided, including screening methods for agents for the treatment of spongiform encephalopathy.

Abstract: This invention provides a nonhuman transgenic mammal carrying transgene comprising the regulatory genes capable of functioning in the hyperacute rejection-occurring local cells and gene encoding human N-acetylglucosaminyltransferase III (GnT-III), or a nonhuman transgenic mammal carrying transgene comprising the regulatory genes and genes encoding GnT-III and the human complement inhibitor. Because of reduced ?-Gal antigens in the hyperacute rejection-occurring local cells or because of both reduced ?-Gal antigens and expression of the human complement inhibitor, the transgenic mammal of this invention can effectively inhibit the hyperacute rejection caused by discordant xenotransplantation. Consequently, this invention provides the transgenic mammal suitable for organ transplantation.

Abstract: A transgenic non-human animal is disclosed, the animal having a nucleic acid inserted in its genome, wherein the presence of the inserted nucleic acid in the genome of the animal results in expression of an agent, which agent is encoded by a nucleotide sequence in the genome of the animal, and wherein the agent inhibits the ability of a leptin to activate an Ob-Rb receptor. Uses of the animal and methods of identifying compounds using the animal are also disclosed.

Abstract: The present invention relates to the use of CD81 protein and polynucleic acid in the therapy and diagnosis of hepatitis C and pharmaceutical compositions, animal models and diagnostic kits for such purposes.

Abstract: The present invention relates to a human artificial chromosome which is genetically transmissible to the next generation with high efficiency and the method for using the same. More specifically, the present invention relates to: a human artificial chromosome in which an about 3.5 Mb to about 1 Mb region containing an antibody ? light chain gene derived from human chromosome 22 is bound to a chromosome fragment which is transmissible to a progeny through a germ line of a non-human animal, said chromosome fragment is derived from another human chromosome; a non-human animal carrying the human artificial chromosome and an offspring thereof; a method for producing the non-human animal; a method for producing a human antibody using the non-human animal or an offspring thereof; and a human antibody-producing mouse carrying the human artificial chromosome.

Abstract: Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the ?:2 and ?:7-subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression pattern of these genes remain largely uninvestigated. The ?2-subunit is the most widely expressed neuronal nicotinic receptors subunit in the nervous system. We have studied the structural and regulatory properties of the 5? sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative and one positive element. The positively acting sequence includes one functional E-box.

Abstract: The present invention relates to a bovine beta-casein gene targeting vector comprising (1) a first region having a length of 5 to 12 kb which is homologous to the promoter and its flanking nucleic acid sequences of bovine beta-casein gene, and comprising exon 1, intron 1, and exon 2 of bovine beta-casein gene; (2) a region for cloning a nucleic acid coding for desired proteins; (3) a region for coding a positive selection marker; (4) a second region having a length of 2.8 to 3.5 kb which is homologous to the nucleic acid sequences of bovine beta-casein gene, and comprising exon 5, 6, 7 and 8, and intron 5, 6 and 7 of bovine beta-casein gene; wherein the nucleic acid segment corresponding to the first region is located upstream to the nucleic acid segment corresponding to the second region in the 5?-3? arrangement of beta-casein gene.

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: A method of producing a transgenic cell comprising introducing into a cell a non-primate lentiviral expression vector comprising a nucleotide of interest (NOI). Also described is a method of producing a transgenic cell comprising introducing into a cell a lentiviral expression vector comprising a NOI capable of generating an antisense oligonucleotide, a ribozyme, an siRNA, a short hairpin RNA, a micro-RNA or a group 1 intron. Also described is a viral vector comprising a first nucleotide sequence, wherein said first nucleotide sequence comprises: (a) a second nucleotide sequence comprising an aptazyme; and (b) a third nucleotide sequence capable of generating a polynucleotide; wherein (a) and (b) are operably linked and wherein the aptazyme is activatable to cleave a transcript of the first nucleotide sequence such that said polynucleotide is generated.

Abstract: We prepared a transgene comprising human HB-EGF precursor cDNA, as a diphtheria toxin receptor gene, at the downstream of an insulin promoter, and introduced this transgene into a mouse fertilized egg, to produce a transgenic mouse of the present invention. In this mouse, human HB-EGF precursors are expressed specifically in islet beta cells, and by injection of diphtheria toxin, islet beta cells are selectively destroyed, resulting in that the mouse shows diabetes two or three days after the injection. This mouse can be utilized in screening and development of new medicines and therapy protocols for diabetes.

Abstract: The present invention is directed to a transgenic non-human mammal (e.g., a rodent such as a mouse) whose genome comprises a recombinant nucleic acid sequence comprising an ?1A-adrenergic receptor (AR) and a marker peptide (e.g., a fluorescent peptide such as green fluorescent protein and an enhanced green fluorescent protein) operably linked to all or a functional portion of an ?1A-AR promoter, wherein the ?1A-AR (e.g., human ?1A-AR) and the marker peptide are expressed as a fusion protein in the transgenic non-human mammal. The present invention also provides methods of producing a transgenic non-human mammal whose genome comprises a recombinant nucleic acid sequence comprising an ?1A-AR and a marker peptide, as well as targeting constructs for use in such methods. The invention also provides a source of cells (for example, tissue, cells, cellular extracts, organelles) and animals useful for elucidating the function of ?1A-AR in intact animals.

Abstract: The invention describes a transgenic non-human animal overexpressing neurotrypsin wherein the animal exhibits symptoms of sarcopenia.