Abstract: The present invention is directed to methods using transgenic mice to screen for biologically active agents.

Abstract: An embryo that is transferred into the uterus of a recipient female is protected from embryotoxic effects of prostaglandin F2? by exposing the embryo to a prostaglandin antagonist.

Abstract: The subject of the present invention is to provide a means to producing an erythropoietin-producing organoid using mesenchymal stem cell derived from a mammal. It is a method for producing erythropoietin-producing organoid (organ-like structure) precursor, comprising the step of transplanting mesenchymal stem cell derived from a mammal into an embryo within a pregnant mammalian host or an embryo separated from a pregnant mammalian host to thereby induce the differentiation of the mesenchymal stem cell, in particular, a site to which the mesenchymal stem cell is to be transplanted is a nephrogenic site of the embryo, and a timing of transplantation corresponds to the stage in which a immune system of the host is still immunologically tolerant.

Abstract: Provided herein are compositions and methods relating to the involvement of RNF5 in muscle wasting.

Abstract: This invention relates to the isolation and propagation of pluripotent cells isolated from the mammalian late epiblast layer, termed Epiblast Stem Cells' (EpiSCs). These cells are useful in a range of applications, including the generation of transgenic animal species.

Abstract: The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. In such knockout mice, bone mineral content, bone mineral density, and bone strength were found to be decreased, and the number of osteoclasts in bone tissues was found to be increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited. Furthermore, administration of purified S1-5 protein to osteoporotic model mice showed that this protein has the effect of improving osteoporosis. The above findings demonstrate that S1-5 protein is useful for treating and preventing age-related diseases such as osteoporosis.

Abstract: The present invention relates to a method of identifying candidate genes and the proteins encoded by them that are useful in the inducement of hybrid vigour, hybrid debility and/or the diagnosis, prognosis and treatment of disease.

Abstract: A vector for creating kf-1 gene knockout nonhuman animals exhibiting increased anxiety-like behaviors, and containing Lox-pM-M-kf-1[in3b]-kf-1[ex4a]-LoxP, (wherein, M is a selection marker gene, pM is a promoter for the expression of the selection marker gene, kf-1[in3b] is a sequence represented by SEQ ID NO: 2, and kf-1[ex4a] is a sequence represented by SEQ ID NO: 3); kf-1 gene knockout nonhuman animals exhibiting increased anxiety-like behaviors produced by using the vector or a descendant of the animal, and a method for use of the same.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

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: The present invention relates to methods, compositions, compounds and kits for detecting, measuring and modulating protein ubiquitylation via the N-end rule pathway and for identifying novel substrates, enzymes and modulators of N-end rule ubiquitylation. The present invention also relates to specific substrates of N-end rule ubiquitylation as well as activated fragments of these substrates, proteases that expose N-degrons in these substrates, ubiquitin ligases that ubiquitylate these substrates and inhibitors of the ubiquitylation of these substrates.

Abstract: The present invention provides a method of producing a genetically engineered transgenic organism, by (a) incorporating into the organism a functional DNA sequence that confers a trait on an organism and (b) incorporating into the organism a non-functional DNA sequence, wherein the non-functional DNA sequence encodes an information message using a predefined coding scheme, wherein the information message provides information about the functional DNA sequence, and the predefined coding scheme can be used to map a plurality of information messages into a plurality of non-functional DNA sequences and additionally, the functional and the non-functional DNA sequence are incorporated into the same chromosome of the organism.

Abstract: A transgenic non-human animal, such as a mouse, has a genome that include a nucleic acid construct having at least one transcriptional regulatory sequence capable of directing expression in B cells of the animal, wherein the transcriptional regulatory sequence is operably linked to a nucleic acid encoding a miR155 gene product. A method of testing the therapeutic efficacy of an agent in treating or preventing a lymphoproliferative condition includes assessing the effect(s) of the agent on a transgenic non-human animal.

Abstract: Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. The present invention provides improved mammary expression cassettes useful for the expression of genes at high levels in the milk of transgenic animals. In particular, the present invention provides recombinant signal peptide sequences derived from a-lactalbumin and aS1-casein milk genes suitable for leading protein secretion in the mammary gland.

Abstract: Methods for controlling insect attraction, as well as inhibiting, preventing and reducing the incidence of insect-borne disease in a subject, are described by inhibiting the expression, activity, dimerization or signaling by gustatory receptors that alter insect responsiveness to carbon dioxide. Methods for identifying agents for effecting the same by interfering with expression, activity, dimerization or signaling by gustatory receptors are also provided.

Abstract: The present invention relates to transgenic mice and isolated transgenic mouse cells, the mice and mouse cells comprising a disrupted H2 class I gene, a disrupted H2 class II gene, a functional HLA class I transgene, and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cells are deficient for both H2 class I and class II molecules, wherein the transgenic mouse comprises a functional HLA class I transgene and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cell has the genotype HLA-A2+HLA-DR1+?2m°IA?°. The invention also relates to methods of using a transgenic mouse of the invention.

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: The present invention provides a genetic engineering material for insects that enables a target protein to be purified easily, without requiring the use of recombinant baculovirus, while simultaneously providing a process for producing exogenous protein using that genetic engineering material. A gene recombinant silkworm is obtained by inserting an exogenous protein gene such as a cytokine gene coupled to a promoter that functions in silk glands into a silkworm chromosome. An exogenous protein such as a cytokine is then extracted and purified from the silk glands or cocoon of that silkworm or its offspring. A large amount of exogenous protein can be produced within silk gland cells, outside silk gland cells or in silk thread or a cocoon by inserting an expression gene cassette, in which the DNA sequence of the 3? terminal portion and the DNA sequence of the 5? terminal portion of fibroin H chain gene are fused to the exogenous protein gene, into silk gland cells and so forth.

Abstract: An object of the invention is to provide a non-human animal which can be utilized as a model animal well exhibiting a pathological condition of low-turnover type of osteoporosis and chronic obstructive pulmonary disease, for screening therapeutic agents for osteoporosis or therapeutic agents for chronic obstructive pulmonary disease, etc. The invention includes a non-human animal, wherein a gene coding for CD9 and a gene coding for CD81 are deficient at least in somatic cells; and a method to use the non-human animal as an osteoporosis model animal, including a step of measuring the degree of inhibition in the osteogenesis, and a method to use the non-human animal as a chronic obstructive pulmonary disease model animal, including a step of measuring the degree of a phenotype similar to chronic obstructive pulmonary disease.

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 describes a transgenic mouse susceptible to neuromuscular disease. The present invention also includes methods for treatment of neuromuscular diseases by interfering with activity between androgen and androgen receptors exclusively in the muscle fibers.

Abstract: Desirable fusion proteins can be produced in and purified from the milk of transgenic animals. The peptides are made as fusion proteins with a suitable fusion partner such as human alpha-fetoprotein. The fusion partner protein acts to promote and increase the half-life of the overall molecule as well as having therapeutic effects on its own. The fusion protein is typically produced through the use of transgenic animals and can be purified away from the now the milk or other bodily fluid of such an animal by an affinity purification method. A particular advantage of producing peptides via this route, in addition to the obvious advantages of high yield and biocompatibility, is that specific post-translational modifications, such as carboxy terminal amidation, can be performed in the mammary gland.

Abstract: Transgenic and cloned ungulates and particularly cloned cattle are disclosed, wherein such cattle contain a deletion or disruption of the prion gene locus and do not express functional prion protein, and are not susceptible to prion-related diseases such as bovine spongiform encephalopy or Mad Cow Disease.

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: The invention relates to mice which are genetically deprived of T, B lymphocytes and NK cells, deficient for murine MHC class I and/or MHC class II molecules, and transgenic for the expression of the HLA class I and/or HLA class II molecules, and to their use as recipient hosts for the transplantation of human haematopoietic precursors, to study the human adaptative immune system development and function in vivo. The invention relates also to the applications of this human/mouse chimera model to improve immunotherapy against pathogens, cancer and autoimmune diseases.

Abstract: This invention relates to the production of dual models of Congenital Heart Defects and Hypertrophic Cardiomyopathy with the use of mice which are genetically modified by transgenic (gene-knockout) techniques. The present invention produces knockout mice that show multiple cardiovascular malformations which will serve as a model of cardiovascular diseases for the screening of potential drugs against ventricular remodeling, malignant arrhythmias, primary pulmonary hypertension, and degenerative valvular diseases, and congenital heart disease.

Abstract: The present invention provides methods of altering gene expression of embryos to provide compositions and methods for efficient generation of transgenic animals. In particular, the present invention provides compositions and methods for generating germ-line transgenic animals by direct injection of nucleic acid molecules into animals.

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 invention provides a human photoaged skin model and an animal model which are useful for evaluating cosmetics and similar products in terms of their anti-aging or rejuvenating effect, as well as a method for producing such a skin model and such an animal model. The method of producing the human photoaged skin model is characterized in that a transplanted skin area of an immunodeficient non-human animal which has undergone transplantation of human skin is irradiated with UV-B light of 80-100 mJ/cm2 for consecutive 4 to 8 weeks, and the irradiated area is left to take its own course for at least 3 weeks. A human photoaged skin model and an animal model produced through this method are also disclosed.

Abstract: This invention provides a model for the induction of immunological tolerance to antigens. The tolerance model of the invention can be used for screening candidate drugs effective in modulating tolerance. The invention also provides the use of such tolerance-modulating drugs as agents for the treatment of chronic illnesses, including chronic viral infections, such as HCV.

Abstract: Disclosed is a nonhuman animal showing the symptoms of human nonalcoholic steatohepatitis which is obtained by transplanting human hepatocytes into an immunodeficient hepatopathic nonhuman animal to produce a chimeric nonhuman animal and then transplanting human hepatocytes that are propagated in the body of the chimeric nonhuman animal into an immunodeficient hepatopathic nonhuman animal of the same species as the immunodeficient hepatopathic nonhuman animal described above, as well as a nonhuman animal showing the symptoms of human fatty liver which is obtained by transplanting human hepatocytes into an immunodeficient hepatopathic nonhuman animal to produce a chimeric nonhuman animal.

Abstract: A transgenic mollusk which can express a desired foreign gene, and a method for producing the same are disclosed. The mollusk is a transgenic mollusk into which a desired foreign gene (excluding a gene giving resistance to a virus) is introduced, which expresses the foreign gene. This transgenic mollusk can be produced by microinjecting into gonad of male and/or female of mollusk a recombinant vector into which a desired foreign gene to be introduced or a nucleic acid containing the foreign gene is inserted; crossing the male and female to produce individuals of first generation; and selecting therefrom (an) individual(s) which express(es) the desired gene.

Abstract: The present invention relates to a method for producing a transgenic non human male animal, preferably a mammal, fish, bird or insect, wherein the transgene(s) confer(s) a change in the transmission ratio of (a) genetic trait(s) to the offspring of said non human male animal, preferably mammal, fish, bird or insect to a non-Mendelian ratio, said method comprising introducing (a) a first nucleic acid molecule encoding an expression product with a Responder function into a chromosome of a non-human germ cell, (fertilized) egg cell, embryonic cell or a cell derived therefrom, of the same species as the transgenic male to be prepared, said chromosome containing or conferring said genetic trait(s), thereby linking on said chromosome said Responder function to the genetic trait(s); and (b) at least one second nucleic acid molecule encoding an expression product with a Distorter function into (a) chromosome(s) of a non-human germ cell, (fertilized) egg cell, embryonic cell or a cell derived therefrom, of the same sp

Abstract: The present invention discloses a non-human animal model for a hereditary autosomal dominant disease. The non-human animal model expresses at least one phenotype associated with the disease and is obtained by a genetic determinant. The invention also relates to sperm cells and embryos comprising the genetic determinant for an autosomal dominant disease. Furthermore, methods for producing the non-human animal model, sperm cell, and embryos are disclosed.

Abstract: The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.

Abstract: The disclosure concerns a method for resistance of epilepsy by suppressing the function of alpha 1G protein of T-type calcium channels, use of suppressor of alpha 1G protein for prevention or treatment for epilepsy, knockout mice resisting epilepsy by disrupting alpha 1G subunit of T-type calcium channel, and preparation method thereof. The ?1G-knockout transgenic mouse can be used for investigating the relationship between diseases particularly neuropathy or psychopathy and the function of ?1G T-type calcium channel via various behavioral tests since ?1G subunit is mainly expression in central nervous system (CNS) and pheripheral nervous system (PNS). Further, the ?1G-knockout transgenic mouse can be used for screening antileptic agents.

Abstract: Methods are disclosed for screening for the occurrence of gene silencing (e.g., post transcriptional gene silencing) in an organism. Also provided are methods for isolating silencing agents so identified.

Abstract: Site-specific recombinases provide a means of efficiently manipulating chromosomal sequences in mammalian cells in culture and in mice. Embryonic stem cells containing recombinase nucleic acid constructs that were expressed in the male germline would simplify current protocols for producing mice bearing homologously recombined alleles that have been secondarily rearranged by a site-specific recombinase, five lines of transgenic mice containing a fusion gene consisting of the mouse protamine 1 gene promoter and the Cre recombinase coding sequence (ProCre nucleic acid constructs) showed high levels of Cre-mediated recombination of the germline, but did not show appreciable recombination in other tissues. In different ProCre strains, between 80% and 100% of the progeny that inherited a Cre target nucleic acid construct from males that were also heterozygous for a ProCre nucleic acid construct inherited the Cre-recombined target.

Abstract: The present invention relates to a transgenic animal having substantially reduced major urinary protein (uMUP) production. The present invention also relates to methods of producing such animals, and to the uses of such animals.

Abstract: The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. Histological analysis in such knockout mice revealed that bone mineral content, bone mineral density, and bone strength were decreased, and the number of osteoclasts in bone tissues was increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited.

Abstract: Genetically engineered conditional knock-out mice having conditional disruption of the Abi1/Hssh3bp1 gene are disclosed along with methods of making and using same.

Abstract: Genetically modified mice and nucleic acid constructs for making the genetically modified mice are described. A first mouse having a gene encoding an activator (such as a Cre recombinase) operably linked to a developmentally-regulated promoter (such as a Nanog promoter) is provided. A second mouse having a toxic responder gene (such as a gene encoding diphtheria toxin A) is provided, where the toxic gene is expressed only in the presence of an activator, Embryos from a mating of the first and the second mouse are provided as host embryos suitable for generating mice from donor cells introduced into the host embryos. Ablating the ICM of a mouse embryo physically, chemically, or genetically is described, as well as making F0 generation mice that are substantially or in full derived from donor cells, employing a host mouse embryo with an ablated or nonproliferating ICM.

Abstract: Compounds, compositions, methods of making, and methods of using analogues of (?)-picropodophyllin, as well as a transgenic animal model and its use for identifying anticancer agents.

Abstract: The invention provides an isolated and purified DNA molecule comprising at least one DNA segment, a biologically active subunit or variant thereof, of a circular intermediate of adeno-associated virus, which DNA segment confers increased episomal stability, persistence or abundance of the isolated DNA molecule in a host cell. The invention also provides a composition comprising at least two adeno-associated virus vectors.

Abstract: The object of this invention is to provide a method for evaluating genetic ability for carcass weight in a bovine individual by using gene markers. According to the method, the nucleotide at the e9 site of the bovine NCAPG gene is determined. When it is G, genetic ability for increasing carcass weight is judged to be higher. Alternatively, the amino acid at the E9 site of the bovine NCAPG gene is determined. When it is methionine, genetic ability for increasing carcass weight is judged to be higher.

Abstract: The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of making and using such animal models in the identification and characterization of therapies for the diseases and conditions.

Abstract: Interfering RNA molecules are now designed and produced with specificity for multiple binding sequences present in distinct genetic contexts in one or more pre-selected target RNA molecules and are used to modulate expression of the target sequences. Such a multitargeting interfering RNA approach provides a powerful tool for gene regulation.

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 provides novel transgenic animal models of reduced dynorphin expression in humans that are useful for identifying compounds that are antagonists, inverse agonists, agonists or mimetics of one or more dynorphin peptide products of preprodynorphin. The compounds identified in such screening assays are useful in contexts related to the treatment of obesity and type II diabetes including, for example, improving weight loss and/or reducing appetite during dieting; treating feeding disorders; and for modifying fat mass and reducing glucose intolerance in males.

Abstract: Methods to introduce genetic material, such as DNA, to embryos, are disclosed. In some embodiments, the method involves preparing the pregnant mother to receive the genetic material into a blood transport vessel which passes to the embryo, avoiding a maternal capillary bed and introducing the material under low pressure so as not to kill the pregnant animal. The effectiveness of the method is such that the nucleic acid has been expressed in all the cells of the embryo and in the postnatal mouse, including the primordial germ cells, thus making the nucleic acid germ line heritable.