Abstract: The present invention provides in a first aspect a mouse in which the ? (lambda) light chain locus has been functionally silenced. In one embodiment, the mouse ? light chain locus was functional silenced by deletion of acne segments coding for the ? light chain locus. In a further aspect, a mouse containing functionally silenced ? and ? (kappa) L chain loci was produced. The invention is useful for the production of antibodies, for example heterologous antibodies, including heavy chain only antibodies.

Abstract: Methods and compositions for producing selected non-human mammalian germ cells and gametes and for making non-human animals using the produced germ cells and gametes are provided by the present invention. Methods of generating a non-human embryo and/or animal derived from donor stem cells, methods of generating chimeric non-human animals having substantially all gametes and/or germ cells derived from the donor stem cells, methods of producing a non-human host embryo lacking functional endogenous germ cells and non-human host embryos incapable of developing endogenous gametes of the present invention are described herein.

Abstract: Provided are methods for determining susceptibility, resistance or tolerance to Mycobacterium avium subspecies paratuberculosis (Map) infection, comprising: determining, using a biological sample from a mammalian subject, a presence or absence of at least one EDN2 gene mutation, or the genotype of at least one EDN2 gene single nucleotide polymorphism (SNP) selected from the SNP group consisting of SNP105 (nucleotide position 105,288,174 on BTA3 (UMD 3.1)), SNP208 (nucleotide position 105,298,664 on BTA3 (UMD 3.1)), and SNP272 (nucleotide position 105,305,070 by on BTA3 (UMD 3.1)), that segregates with resistance and/or tolerance to Map tissue infection; and determining, based thereon, at least one of susceptibility, resistance or tolerance of the mammalian subject to Map infection. Additionally provided are mammals (e.g., bovine) derived culling, selecting, or selective breeding, based on disclosed methods, and methods for procuring mammals.

Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.

Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

Abstract: The invention discloses novel model of transgenic mammal, a method of crossbreeding transgenic mammal and the use of the transgenic mammal for assessing prevention and/or treatment methods for cardiovascular and other diseases related to lipoprotein(a). The transgenic mammal expresses human apolipoprotein (a) (apo(a)) and human apolipoprotein B-100 (apo B-100) genes and produces human lipoprotein (a), apo (a) and apo B-100 and produces no vitamin C. This novel dual transgenic mammal is the ideal model for testing pharmaceutical compounds for efficacy and usefulness in the prevention and/or treatment of human diseases.

Abstract: The present invention provides a CD81 and OCLN double transgenic mouse and its construction method and use. The double transgenic mouse can be used to constitute acute and chronic HCV infection in a mouse model.

Abstract: Described herein is the generation of Fah+/? heterozygote pigs by homologous recombination and somatic cell nuclear transfer, and a method for producing Fah?/? homozygote pigs. The Fah-deficient pigs of the disclosure can be used for a variety of research and therapeutic purposes, such as for the expansion of human hepatocytes, and as large animal models of hereditary tyrosinemia type 1, cirrhosis and hepatocellular carcinoma.

Abstract: The present invention relates to transgenic fluorescent orange ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

Abstract: The invention discloses novel model of transgenic mammal, a method of crossbreeding transgenic mammal and the use of the transgenic mammal for assessing prevention and/or treatment methods for cardiovascular and other diseases related to lipoprotein(a). The transgenic mammal expresses human apolipoprotein (a) (apo(a)) and human apolipoprotein B-100 (apo B-100) genes and produces human lipoprotein (a), apo (a) and apo B-100 and produces no vitamin C. This novel dual transgenic mammal is the ideal model for testing pharmaceutical compounds for efficacy and usefulness in the prevention and/or treatment of human diseases.

Abstract: The invention discloses novel model of transgenic mammal, a method of crossbreeding transgenic mammal and the use of the transgenic mammal for assessing prevention and/or treatment methods for cardiovascular and other diseases related to lipoprotein(a). The transgenic mammal expresses human apolipoprotein (a) (apo(a)) and human apolipoprotein B-100 (apo B-100) genes and produces human lipoprotein (a), apo (a) and apo B-100 and produces no vitamin C. This novel dual transgenic mammal is the ideal model for testing pharmaceutical compounds for efficacy and usefulness in the prevention and/or treatment of human diseases.

Abstract: The present invention relates to transgenic green ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

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 inventors produced transgenic silkworms which comprise a promoter of a DNA encoding a protein specifically expressed in the silk gland and a DNA encoding a recombinant antibody whose expression is regulated directly or indirectly by the promoter, and which secrete the recombinant antibody into the silk gland. The recombinant antibodies produced from the silk gland of the transgenic silkworms were confirmed to be active.

Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.

Abstract: Described are transgenic animals for conditional and inducible cell targeting, that express a dimerizable conditional-STOP caspase 3 transgene.

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: The present invention relates to a non human model animal for ulcerative colitis and its main complications such as primary sclerosing cholangitis and colorectal cancer. More particularly, the present invention relates to a transgenic non human animal model for ulcerative colitis and its main complications such as primary sclerosing cholangitis, and colorectal cancer comprising a targeted disruption in the IL10 and NOX1 genes so that IL10 and NOX1 are not expressed in said animal.

Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.

Abstract: The invention discloses a method for controlling fish reproduction, the method comprises the following steps of: A, constructing a recombinant gene CMV-eGFP-SV40-CMV-Ga14-SV40 and establishing a GAL4 transgenic zebrafish line; B, constructing a recombinant gene CMV-RFP-SV40-UAS-antisense dnd and establishing a uas-antisensednd transgenic zebrafish line; and C, hybridizing by taking homozygous transgenic fish of the two lines as parents, and the hybrid generation fish was sterility. The method of the present invention takes a strategy that two fertilizable lines hybridized but hybrid generation is sterility, establishing a novel method with a universal meaning for controlling fish fertility; The method solves the contradiction of the reproductively sterility of fish and the hereditability of characters in a reproduction operation research and can be effectively applied to cultivation of new fish specie and population control.

Abstract: Pentameric CRP is produced at a high efficiency by transferring DNA, which encodes monomeric CRP, into a silkworm to thereby construct a transgenic silkworm and then collecting and purifying pentameric CRP that is produced by the transgenic silkworm constructed above.

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: Genetically modified mammals are described which lack the mannan binding lectin associated serine protease MASP-2, together with methods and constructs for their production. Such mammals are useful as models for disorders of the complement system, and in the identification of treatments for such disorders. Also described are mammals which lack the associated protein MAp19; such mammals may also lack MASP-2.

Abstract: The invention relates to organisms and compositions comprising one or more stem cells or one or more embryos, wherein the one or more stem cells or one or more embryos comprise one or more of the following mutations: (i) a deletion mutation; (ii) a knockout mutation; and/or (iii) an addition of a heterologous nucleic acid sequence; wherein the one or more mutations of (i), (ii), and/or (iii) are site-specific mutations caused by a Xanthomonas TAL nuclease (XTN). The invention also relates to method of mutating an embryo, iPS cell, stem cell, or more particularly a spermatogonial stem cell by exposing the nucleic acid sequence contained within such embryos or cell with a Xanthomonas TAL nuclease.

Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Abstract: This invention provides a biological selective breeding technique in preparation of a transparent zebrafish, Citrine. The appearance of Citrine is transparent and yellowish, with uniformly pigmented black eyes and its inner organs are observable by eyes. The invention also provides a method for in vivo observation of progression and expansion of various disease stages or physiological processes.

Abstract: Mice comprising a human p16 transgene operably linked to an inducible promoter and capable of controlled expression of p16 are provided. Also provided are cells, tissues, and organs obtainable from such mice, and methods for producing p16 transgenic mice.

Abstract: The present invention embraces a transgenic mouse whose genome harbors a nucleic acid molecule encoding caveolin-1 fused in-frame with a reporter. To control expression of the Cav1-reporter, the nucleic acid molecule further includes a selectable marker expression cassette flanked by recombinase target sites in such a manner that, upon exposure to recombinase, said selectable marker expression cassette is excised from said nucleic acid molecule.

Abstract: The present invention relates to transgenic blue ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

Abstract: The present invention relates to the method and use of fluorescent proteins in making purple transgenic fluorescent fish. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing. Thus, new varieties of ornamental fish of different fluorescence colors from a novel source are developed.

Abstract: The present invention relates to the method and use of reef coral fluorescent proteins in making transgenic red, green and yellow fluorescent zebrafish. Preferably, such fluorescent zebrafish are fertile and used to establish a population of transgenic zebrafish and to provide to the ornamental fish industry for the purpose of marketing. Thus, new varieties of ornamental fish of different fluorescence colors from a novel source are developed.

Abstract: Methods and compositions for producing selected non-human mammalian germ cells and gametes and for making non-human animals using the produced germ cells and gametes are provided by the present invention. Methods of generating a non-human embryo and/or animal derived from donor stem cells, methods of generating chimeric non-human animals having substantially all gametes and/or germ cells derived from the donor stem cells, methods of producing a non-human host embryo lacking functional endogenous germ cells and non-human host embryos incapable of developing endogenous gametes of the present invention are described herein.

Abstract: This invention relates to a transgenic animal model for testing immunogenicity and protective efficacy of human vaccines and the method for generating such a multi-transgenic animal. This invention also relates to methods for screening compositions for human vaccine development. More specifically, the present invention relates to a mouse model capable of expressing human leukocyte antigens DR4 and A2, and/or human costimulatory molecules (CD80) which upon infusion of human HLA-matched hematopoietic stem cells develop a functional human immune system able to respond to vaccination with human vaccines. The invention also relates to method of producing human antibodies specific for a desired antigen using the transgenic mouse.

Abstract: Evidence indicates dysregulation. of the immunoregulatory molecule CD45 occurs in Alzheimer's disease (AD). Transgenic mice overproducing amyloid-? peptide (A?) and deficient in CD45 (PSAPP/CD45?/?) recapitulate AD neuropathology. Increased cerebral intracellular and extracellular soluble oligomeric and insoluble A?, decreased plasma soluble A? increased microglial neurotoxic cytokines TNF-? and IL-1?, and neuronal loss were found in PSAPP/CD45?/? mice compared with CD45-sufficient PSAPP littermates. After CD45 ablation, in vitro and in vivo studies demonstrate a microglial phenotype whereby microglia phagocytose less A? but display proinflammatory properties. This microglial activation occurs with elevated A? oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP/CD45?/? mice.

Abstract: A transgenic animal other than human in which neuropsychiatric disorder condition is developed by the deletion of an HB-EGF gene is obtained. The present invention relates to a transgenic animal other than human in which an HB-EGF gene is deficient and neuropsychiatric disorder condition is developed, and a production method thereof, and a method for screening a therapeutic agent for neuropsychiatric disorder. As a transgenic animal in accordance with the present invention, a transgenic animal in which an HB-EGF gene is specifically deficient in the spiny neurons (striatum, and hippocampus) can be obtained by crossbreeding a transgenic animal that contains a genotype of Gng7(+/cre), and a transgenic animal that contains a genotype of Hb-egf(flox/flox).

Abstract: This present invention relates to transgenic animals useful to study human diseases. Specifically, the invention relates to transgenic animals expressing at least two human proteins (optionally in replacement of the counterpart proteins in the animal) whereas a first human protein interacts with a second human protein. The transgenic animals can then be used for evaluating drugs or building disease models that are related to the expressed human proteins in the animals. The animals and methods disclosed herein reduce the possibility identifying a false-positive compound—the compound that show an effect in a naturally-occurring, non-transgenic animal but may not necessarily work or be therapeutic in human, since the compound may only interrupt the interaction between two animal proteins not necessarily two related human proteins.

Abstract: Pentameric CRP is produced at a high efficiency by transferring DNA, which encodes monomeric CRP, into a silkworm to thereby construct a transgenic silkworm and then collecting and purifying pentameric CRP that is produced by the transgenic silkworm constructed above.

Abstract: Hairless, immunodeficient mice on a non-obese diabetic (NOD) background and methods for their production are disclosed herein. The mice are hairless and have multiple immunodeficiencies, including B-cell and T-cell deficiencies, as well as impaired macrophage and complement function. The mice also have a further deficit in natural killer and dendritic cells of the immune system. The mice are useful for biomedical research, for example, in studies involving xenograft transplantation, spontaneous tumors, cancer cell tumorigenesis, tumor angiogenesis, tumor metastatic potential, tumor suppression therapy, carcinogenesis regulation, and tumor imaging.

Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Abstract: Described herein is the generation of Fah+/? heterozygote pigs by homologous recombination and somatic cell nuclear transfer, and a method for producing Fah?/? homozygote pigs. The Fah-deficient pigs of the disclosure can be used for a variety of research and therapeutic purposes, such as for the expansion of human hepatocytes, and as large animal models of hereditary tyrosinemia type 1, cirrhosis and hepatocellular carcinoma.

Abstract: The present invention provides PiggyBac transposase proteins, nucleic acids encoding the same, compositions comprising the same, kits comprising the same, non-human transgenic animals comprising the same, and methods of using the same.

Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized ?2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Abstract: The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

Abstract: The present invention directs to a transgenic NRIP knockout mouse, the genome of which is manipulated to comprise a disruption of a nuclear receptor interaction protein (NRIP) gene, wherein the NRIP gene is disrupted by deletion of exon 2, the mouse exhibits a phenotype comprising abnormal muscular function. The present invention also directs to a method for making a transgenic NRIP knockout mouse whose genome comprises a homozygous disruption of the NRIP gene, the mouse exhibits abnormal muscular function.

Abstract: A double transgenic non-human animal, in particular a transgenic mouse encoding Qpct proteins, which have been implicated in Qpct-related diseases, and Amyloid Precursor Protein (APP). Also provided are cells and cell lines comprising transgenes encoding for Qpct and APP. Also provided are methods and compositions for evaluating agents that affect Qpct, for use in compositions for the treatment of Qpct-related diseases.

Abstract: A method of inducing male and/or female infertility in a genetically modified (GM) fish is disclosed. Also disclosed is a method of generating an infertile GM fish with a phenotype and/or genotype of interest. The method involves generation of a GM fish whose genome comprises a foreign transgene operably linked to a fish gonad-specific promoter selected from the group consisting of an ovary-specific promoter and a testis-specific promoter. The transgene comprises a suicide gene selected from the group consisting of a reductase and a photosensitizer, in which the reductase is operably linked to a reporter gene. Infertility of the GM fish is induced if the GM fish expressing the reductase is treated with an effective amount of a reductase-activated cytotoxic prodrug or if the GM fish expressing the photosensitizer is treated with light irradiation.

Abstract: A process for generating transgenic animals using recombinant lentiviruses. The process comprises injecting recombinant lentiviruses into the interstituim of the testis of a male to produce mature spermatozoa within a few days. The male with transgene expressing lentivirus is mated with a female, forming a progeny carrying the transgene.

Abstract: The present invention provides in a first aspect a mouse in which the ? (lambda) light chain locus has been functionally silenced. In one embodiment, the mouse ? light chain locus was functional silenced by deletion of gene segments coding for the ? light chain locus. In a further aspect, a mouse containing functionally silenced ? and ? (kappa) L chain loci was produced. The invention is useful for the production of antibodies, for example heterologous antibodies, including heavy chain only antibodies.

Abstract: The invention provides transgenic rodents, particularly mice, expressing truncated versions of the Disrupted-in-Schizophrenia-1 (DISC1) gene and showing Schizophrenia-related neural and behavioral phenotypes. The rodents of the invention have (1) a plurality of copies of a heterologous truncated Disc1 genomic DNA sequence which includes at least 1 stop codon after exon 8 such as to encode a Disc1 polypeptide truncated before exon 9; (2) 2 copies of endogenous Disc1 genomic DNA sequence encoding full length Disc1 polypeptide. Also provided are related materials and methods.

Abstract: Disclosed herein are an ?1/CaV3.1 double knockout mouse or ?1?/?; Emx1-Cre mouse with enhanced essential tremor and a screening method of therapeutic agents for essential tremor by using the same. The ?1/CaV3.1 double knockout mouse or ?1?/?; Emx1-Cre mouse of the present invention may be usefully used for development of therapeutic agents for essential tremor because the mouse exhibits essential tremor strong and evident enough to be visually confirmed, compared to an ?1 knockout mouse.