Abstract: The present invention is a porcine animal, tissue, organ, cells and cell lines, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha1,3GT). These animals, tissues, organs and cells can be used in xenotransplantation and for other medical purposes.

Abstract: The c-Jun NH2-terminal kinase (JNK) group of MAP kinases are activated by exposure of cells to environmental stress. The role of JNK in the brain was examined by targeted disruption of the gene that encodes the neuronal isoform JNK3. It was found that JNK3 is required for the normal response to seizure activity. Methods of screening for molecules and compounds that decrease JNK3 expression or activity are described. Such molecules or compounds are useful for treating disorders involving excitotoxicity such as seizure disorders, Alzheimer's disease, Huntington disease, Parkinson's disease, and ischaemia.

Abstract: Use of PON gene cluster in preparing medicament for treating atherosclerosis in mammals, wherein the PON gene cluster treat atherosclerosis by promoting stability of atherosclerotic plaque. Method for the developing PON gene cluster transgenic mouse model and use of PON gene cluster in the development of PON gene cluster positive transgenic mouse model with atherosclerosis are also provided.

Abstract: A conditional knock-out non-human animal is disclosed. Wherein some cells of the non-human animal but not all the cells comprise a disrupted MO-1 nucleic acid sequence, wherein the disruption results in an inability of the non-human animal to produce detectable levels of the MO-1 protein, as assayed by Southern blot analysis.

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 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 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: 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: The present invention provides systems that allow reliable multiplexed transformation of Drosophila embryos. The present invention provides methods and reagents that allow preparation of injection-quality nucleic acid samples and that allow simultaneous preparation of multiple such samples. The present invention provides systems for simultaneous processing of multiple injected embryos. The present invention provides methods for transformation of Drosophila embryos involving use of virginator strains that can be used to increase the efficiency of setting up the crosses needed to produce the eggs for the injections and for the crosses needed to screen for transformants.

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: Immunocompromised rodents that have been modified to express a fluorescent protein in substantially all tissues are described. These rodents are useful as models for gene expression, tumor progression and angiogenesis. Also provided are model systems where heterologous tissues fluorescing in a first color are transplanted into hosts that have been modified to fluoresce in substantially all tissues with a second color.

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 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 present invention provides novel methods of maintaining genetic stability of non-human animal inbred strains. In the methods, pedigree-tracked cryopreserved embryos derived from a foundation colony are produced and used to re-establish the foundation colony at appropriate intervals.

Abstract: The present invention discloses nucleic acids, proteins, and antibodies for SALL4 (including isoforms SALL4A, SALL4B, and SALL4C), a zinc finger transcriptional factor. Further, methods are disclosed which demonstrate that constitutive expression of SALL4 increases leukemogenic potential in cells of model animal systems. Moreover, constitutive expression of select isoforms (e.g., SALL4B) in transgenic mice demonstrate that these animals develop myelodysplastic syndrome (MDS)-like signs and symptoms, including subsequent acute myeloid leukemia (AML), which is transplantable. The disclosure also provides methods for identifying and purifying embryonic stem cells, adult stem cells, cancer stem cells, including leukemia stem cells, methods for identifying substances which bind to and/or modulate SALL4, methods for diagnosing MDS in a subject, and methods of treating a subject presenting MDS.

Abstract: Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.

Abstract: Embodiments of the present invention describe a novel and versatile inducible binary expression system (the ‘Q system’) and methods for controlling transgene expression in vitro and in vivo, for lineage tracing, for genetic mosaic analysis and for determining gene function.

Abstract: Silkworms which have (i) a DNA encoding a transcriptional regulator operably linked downstream of a promoter of a DNA encoding a protein specifically expressed in the silk gland and (ii) a DNA encoding TRACP5 operably linked downstream of a target promoter of the transcriptional regulator were produced. The result showed that active TRACP5b was produced from the silkworms. This means that TRACP5 produced from the silk gland of the silkworms undergoes processing in the silk gland that is similar to the processing taking place at bone resorption sites.

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: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: This invention provides methods for producing antibodies, wherein the methods comprise the step of administering an immunogen comprising both a target antigen and a background antigen to transgenic animals, into which a gene coding for the background antigen has been introduced. Since immunotolerance to the background antigens have thus been induced in the transgenic animals, the animals efficiently produce antibodies to target antigens.

Abstract: The invention relates to a method for generating a transgenic organism. The invention also relates to a method for detecting and characterizing a genetic mutation in a transgenic organism. The invention further relates to a method for isolating a gene which is correlated with a phenotypic characteristic in a transgenic animal. The invention further relates to a method for isolating an exon in a transgenic animal. The invention also relates to a method for modulating the expression of a gene in an organism.

Abstract: The invention provides compositions and methods for the generation of novel non-human transgenic animals which contain an alteration in a gene of interest. These transgenic animals are capable of generating antibodies, e.g., human monoclonal antibodies, specific for the product of a gene of interest that has been functionally disrupted in the transgenic animal. Furthermore, the methods and compositions of the invention are suitable for use in the treatment, diagnosis, and imaging of disease.

Abstract: An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI?/?) and an impaired ApoE expressor (Apoeh/h) to generate a strain referred to as Apoeh/hSRB1?/? mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The Apoeh/hSRB1?/? mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge.

Abstract: The present invention provides for monitoring of NF-?B-associated inflammation in mice undergoing Id-driven autoimmune disease. The mice are triple transgenic mice expressing both Id+ B cells and Id-specific CD4+ T cells as well as a luciferase reporter transgene under NF-?B control. NF-?B activation and nuclear translocation of NF-?B, luciferase activity are repeatedly monitored in intact mice by whole body bioluminescence imaging. Results are corroborated at the cellular level by detection of luciferase protein expression in single cells. The results show that imaging of NF-?B activation permits early detection of subclinical disease as well as tracking of disease development.

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

Abstract: Disclosed herein are homozygously modified organisms and methods of making and using these organisms.

Abstract: Provided are methods for controlling endogenous gene expression comprising control of the DNA methyltransferase (Dnmt1) for modulation of DNA methylation and epigenetic mechanisms. Provided are transcriptional regulatory systems involving multiple (e.g., three) exogenous binary systems, lacI, tetR and Gal4, for reversible up/down regulation of endogenous target genes Provided are lac operator and repressor modifications for improved repression relative to wild type (WT) lac and tet systems. Provided are endogenous Dnmt1 promoter modifications, comprising targeted lac operator sequences that do not significantly alter promoter activity absent repressors, yet show substantially reduced expression of the targeted allele upon lac repressor introduction. The lacO targeted Dnmt1 allele is introducible into the mouse germline, to provide a respective upregulatable transcriptional control system in vivo (e.g.

Abstract: It is an object of the present invention to provide a non-human gene-disrupted animal with a disrupted ADAM11 gene. According to the present invention, a non-human gene-disrupted animal, wherein either one of or both alleles of an ADAM11 gene are disrupted, is provided.

Abstract: The invention relates to novel non-human transgenic animals, which upon antigenic stimulation are capable of producing monovalent antibodies binding to a selected antigen, modified heavy chain transgenes, methods for producing the non-human transgenic animals, methods for immunizing the non-human transgenic animals for as well as monovalent antibodies obtainable by such immunization methods.

Abstract: The present invention relates to a combination of DNA segments comprising: (a) a first segment comprising in 5? to 3? or 3? to 5? order: (aa) a promoter; (ab) a first DNA sequence comprising: (i) a DNA sequence giving rise upon transcription to the sense strand of an shRNA molecule; (ii) a transcriptional stop element which is flanked by a first type of recombinase recognition sequences; and (iii) a DNA sequence giving rise upon transcription to the antisense strand of an shRNA molecule; (b) a second segment comprising in 5? to 3? or 3? to 5? order: (ba) a promoter; (bb) a second DNA sequence comprising: (i) a DNA sequence giving rise upon transcription to the sense strand of an shRNA molecule; (ii) a transcriptional stop element which is flanked by a second type of recombinase recognition sequences; and (iii) a DNA sequence giving rise upon transcription to the antisense strand of an shRNA molecule; wherein (i) said first type of recombinase recognition sequences are recognized and recombined by a recombinas

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 present invention relates to genetically altered hybridomas, myelomas and B cells. The invention also relates to utilizing genetically altered hybridomas, myelomas and B cells in methods of making monoclonal antibodies. The present invention also provides populations of hybridomas and B cells that can be utilized to make a monoclonal antibody of interest.

Abstract: This invention relates to a method for humanising a mouse. In particular, the invention relates to a method for replacing a cluster of mouse genes with single or multiple genes from the corresponding human cluster using a combination of homologous recombination and site-specific recombination.

Abstract: The present invention relates generally to chemical-inducible system and to methods of use in transgenic animals. More specifically, the present invention relates to a chimeric transcription factor that binds to a ligand and functions in ligand-dependent manner to induce expression of genes of interest under the control of a synthetic operator-promoter sequence. The expression of genes of interest can be tightly controlled by adding or removing the ligand.

Abstract: Disclosed herein are an ?1/CaV3.1 double knockout mouse or ??/?;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 ca knockout mouse.

Abstract: The invention provides compositions and methods for the generation of novel non-human transgenic animals which contain an alteration in a gene of interest. These transgenic animals are capable of generating antibodies, e.g., human monoclonal antibodies, specific for the product of a gene of interest that has been functionally disrupted in the transgenic animal. Furthermore, the methods and compositions of the invention are suitable for use in the treatment, diagnosis, and imaging of disease.

Abstract: A transgenic non-human mammal with a disruption in its IL-21 receptor gene is provided, along with methods of using the transgenic non-human mammal.

Abstract: Provided are methods for determining resistance or tolerance of a subject to Mycobacterium avium subspecies paratuberculosis (Map) infection, comprising determining, a presence or absence of a mutation, or the genotype of a single nucleotide polymorphism (SNP) within Map infection linkage disequilibrium region SEQ ID NO:46 that segregates with resistance or tolerance to Map infection, or determining a presence or absence of a mutation or a genotype of a SNP within a Map infection linkage disequilibrium region (SEQ ID NO:1) that is in linkage disequilibrium therewith, and determining, based thereon, susceptibility, resistance or tolerance of the subject to Map infection. In particular aspects, a presence or absence of a mutation, or the genotype of a single nucleotide polymorphism (SNP) within at least one gene selected from the group consisting of HIVEP3; EDN2; and LOC521287 that segregates with resistance or tolerance to Map tissue infection is determined.

Abstract: Disclosed are transgenic fish, and a method of making transgenic fish, which express transgenes in stable and predictable tissue- or developmentally-specific patterns. The transgenic fish contain transgene constructs with homologous expression sequences. Also disclosed are methods of using such transgenic fish. Such expression of transgenes allow the study of developmental processes, the relationship of cell lineages, the assessment of the effect of specific genes and compounds on the development or maintenance of specific tissues or cell lineages, and the maintenance of lines of fish bearing mutant genes.

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: This invention relates to a method for stably expressing a transgene integrated into the genome of an animal cell or of an animal over a long period. Specifically, this invention provides: an approximately 2.5 kb XhoI-BamHI fragment (or XB fragment) derived from the Evx2-Hoxd13 intergenic region of the animal genome, or a homologue thereof; a DNA containing a foreign DNA wherein the DNA has been inserted between the two essentially identical XB fragments or homologues thereof; a vector, animal cell, or nonhuman mammalian animal containing said DNA; and use of the vector, animal cell, or nonhuman mammalian animal for production of a substance or therapy.

Abstract: The present invention provides a method of producing a non-human vertebrate that harbours germ cells having a desired gene transferred thereto, comprising injecting the desired gene to the testis of a non-human vertebrate wherein no tight junction exists between Sertoli cells to transfer the desired gene to germ cells, so as to obtain a non-human vertebrate that harbours the germ cells having the desired gene transferred thereto. Using the method of the present invention, even in animal species and lines for which in vitro transduction has been difficult to date, it is possible to obtain an individual harbouring germ cells, particularly spermatogonial stem cells, having a desired gene transferred thereto, at extremely high efficiency.

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: A transgenic non-human animal whose genome comprises a stable integration of a transgene that encodes at least one Fas-ligand protein operably-linked to a tetracycline-inducible promoter includes cells that express the transgene and undergo apoptosis. The transgenic non-human animal can be used to screen for compounds that inhibit apoptosis and to identify cells that are capable of differentiating in vivo.

Abstract: The invention relates to production of maladapted animals characterized by PTSD like behavior from a population by behavioral conditioning. The method includes determining a baseline behavioral level for individual under defined conditions; exposing each individual animal to trauma event and further determining a posttraumatic event behavioral level; re-exposing each individual to a trauma related event and further determining an individual post trauma related event behavioral level and evaluating the individual post trauma related event behavioral level for each individual animal with respect to a baseline value according to a predetermined rule in order to determine which individuals are maladapted animals characterized by PTSD like behavior. Use of the method for assaying efficacy of PTSD treatment is within the scope of the invention, as are animals produced by claimed methods. Once the method is established, biological parameters may be employed in addition to, or in lieu of behavioral parameters.

Abstract: A double-inducible system for expressing a transgene, preferably comprising an RU486-inducible system integrated with a CID-inducible system. The invention further comprises a gene expression system for use in in vitro cell culture studies, and a gene expression expression system for use in engineering modified bigenic mice.

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 is directed to a hairless, immunodeficient mouse that is homozygous recessive for a hairless (Hrhr) allele and both B-cell deficient and T-cell deficient. The B-cell and T-cell deficiency is attributed to a homozygous recessive scid allele (Prkdcscid), a homozygous recessive beige allele (Lystbg), or a mutated Rag allele. These mice offer an advantage over nude mouse models used in cancer research because they can be maintained as homozygous breeding pairs and they have greater immune deficits, which permit better growth of xenogenic tumor lines, and rapid assessment of cutaneous and subcutaneous tumors and tissue grafts.

Abstract: Provided herein are methods and compositions related to viral vectors. Also provided herein are methods and compositions for the efficient transfection of a host, for example through the highly efficient lentivector delivery system, and for the exquisite control of the timing and level of expression of the transferred sequence of interest by the simple administration of a modulator to the host harboring the transferred sequence of interest. Also disclosed are methods of making transgenic mice and transgenic mice made using compositions and methods relating to viral vectors.