Abstract: Disclosed are compositions and methods for imaging in animals.

Abstract: Triple Tg (megsin/RAGE/iNOS-Tg) was created by crossing megsin-Tg with RAGE/iNOS-Tg. The megsin/RAGE/iNOS-Tg develops marked pathologies of diabetic nephropathy unfound in conventional models at early stages, and various pathological conditions such as glomerular hypertrophy were observed uniformly in the megsin/RAGE/iNOS-Tg mice. In addition, it was also found that animals exhibiting these symptoms were useful as a disease model animal for diabetic nephropathy. Specifically, the disease model animals of the present invention overexpress the megsin gene, a gene encoding the receptor for advanced glycation end-products, and an inducible nitric oxide synthase gene. As a result, accompanying kidney function disorders of glomerular failure develop at early stages.

Abstract: Provided are previously uncharacterised enhancer elements from the preprotachykinin-A (PPTA) which shows transcriptional enhancement activity in Substance P (SP) expressing cells. These are termed ECR1 and ECR2. The invention provides nucleic acids comprising these sequences and variants or fragments thereof, plus methods and materials based thereon, such as transformed host cells, transgenic animals, and screening and expression systems.

Abstract: The invention provides peptides and the nucleic acid sequences that encode them. The invention further provides therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders.

Abstract: The invention relates to a transgenic mouse model with deficient respiratory chain function in dopamine (DA) neurons. By suppressing or deleting the mitochondrial transcription factor A (Tfam) in DA neurons, a mouse model is obtained, which reproduces key pathophysiological features of Parkinson's disease (PD), i.e., slow progressive loss of DA terminals in striatum and loss of DA neurons in substantia nigra pars compacta; alpha-synuclein immunoreactivity including intracellular inclusions similar to Lewy bodies in affected areas prior to and during cell loss; progressive movement disorder associated with abnormal gait, tremor and rigid limbs. The mouse model can be used to develop pharmacological, gene therapy or cell therapy treatments for PD.

Abstract: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Abstract: The invention features novel methods for the production of large quantities of xenogenous antibodies, such as human antibodies. Preferably, this result is effected by inactivation of IgM heavy chain expression and, optionally, by inactivation of Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of xenogenous antibodies (e.g., non-bovine antibodies), preferably human antibodies.

Abstract: The present invention is directed, at least in part, to mice which express exogenous complement receptor type 1 (CR1) on red blood cells. The invention also pertains to genetic constructs encoding heterologous CR1 for expression on red blood cells. Methods of using the transgenic animals of the invention to identify and/or evaluate compositions that can reduce the concentration of an agent, e.g., a biologic agent, in the serum, circulation and/or tissues of a subject are also provided.

Abstract: A transgenic non-human aquatic organisms, such as piscine, crustacean, mollusks, and the like, having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the aquatic organism is disclosed. Also disclosed are methods for making such organisms and nucleic acid sequences encoding GDF-8 polypeptides from such aquatic organisms.

Abstract: The present invention relates to transgenic non-human animals, tissues or cells derived therefrom and methods of producing them. The transgenic non-human animals or tissues or cells derived therefrom provide a system capable of expressing human proteins responsible for drug metabolism in place of the homologous endogenous non-human animal proteins and for the controlled expression of human genes introduced into the animal so that the expression of the human genes is regulated in a manner more closely analogous to that seen in vivo in humans.

Abstract: The present invention relates to a composition for screening antihypertensive drugs, which contains a mammalian TCTP gene or a protein expressed therefrom, as well as a method for screening antihypertensive drugs using the composition. TCTP contained in the inventive composition acts as a cytoplasmic inhibitor of the Na/K APTase pump, thus causing hypertension and heart hypertrophy. Therefore, the inventive composition and the screening method using the same will be useful for the investigation and development of antihypertensive drugs. Furthermore, the inventive TCTP-overexpressing transgenic mice shows hypertension or heart hypertrophy as a phenotype. Thus, the inventive transgenic mice will be useful in screening test substances developed for the treatment and improvement of hypertension and heart hypertrophy, by administering the test substance to the transgenic mice and observing the extent of treatment and improvement.

Abstract: The present invention provides an improved method for achieving efficient transcription and translation of modified transgene constructs in vector systems. The vector may be a lentiviral vector. Such a method facilitates the production of viral vector genomes with intact functional transgene sequences allowing stable integration of a transgene-containing viral vector genome into the germline of an animal such as a transgenic avian. The subsequent expression of the transgene results in a recombinant protein product being produced, which, in the case of a transgenic avian can result in the targeted production of the protein into the egg of the transgenic bird.

Abstract: Methods are provided to increase resistance to cell damage in a subject. The increase in resistance to cell damage in a subject in the subject is accomplished by decreasing activity of eEF2 kinase in the subject. The eEF2 kinase activity can be decreased by decreasing the amount of functional eEF2 kinase produced by the subject, including contacting the eEF2 kinase with a compound that inhibits phosphorylation of eEF2 kinase substrate or decreasing the amount of functional eEF2 kinase is decreased by reducing expression of a gene encoding the eEF2 kinase.

Abstract: An amphidiploid aquatic animal according to the present invention has genomes AB of different species and carries fertile XXXY sex chromosomes. Among a large number of aquatic animals of the first filial generation kept in a closed system, a nonreductive sperm of a male and a nonreductive egg of a female are selected. Then the nonreductive egg is fertilized with the nonreductive sperm to create an amphidiploid aquatic animal having fertile XXXY sex chromosomes. Since this amphidiploid has the XXXY sex chromosomes, it can be crossed with an egg AXBX of an F1 hybrid that produces nonreductive eggs, thus ensuring a stable creation of amphidiploids in the subsequent generations by natural crossbreeding. In the meiotic division, one set of the chromosomes of each species is assuredly distributed to each gamete. Therefore, the trait of the first generation (F1) will be perpetually maintained.

Abstract: To comprehensively modify genome, it is intended to develop a transposition system of the copy and paste type which has an improved efficiency. This object has been achieved by the finding that an LTR retrotransposon is partly usable in a transposition system. Namely, a technique of efficiently transferring a foreign gene into a cell by using a transposon. More specifically speaking, a complete IPA element and a functional promoter sequence are found out. It is clarified that, without a combination of them, a retrotransposon cannot exert its function.

Abstract: The present invention relates to a nucleic acid molecule encoding a K94A/K447A mutant of wild type p90 ribosomal S6 kinase (p90RSK) and DNA constructs, expression vectors, and hosts including the mutant p90RSK-encoding molecule. The present invention also relates to two transgenic non-human animal models of ischemic reperfusion (I/R) damage, the first animal having a transgene encoding a mutant p90RSK that is rendered kinase inactive for S703 phosphorylation of NHE1 and the second animal having a transgene encoding for cardiac-specific overexpression of wild type p90RSK in the animal that provides a model for diabetic cardiomyopathy. Also provided are methods for generating transgenic non-human animal models of ischemic reperfusion (I/R) damage; for using the transgenic cells for identifying an agent capable of inhibiting p90RSK-induced I/R damage; for identifying agents that modulate I/R injury resulting from an ischemic event; and for treating individuals to inhibit I/R injury following an ischemic event.

Abstract: Disclosed is a transgenic knockout mouse whose genome comprises a homozygous disruption in its endogenous FcRn gene. The homozygous RcRn disruption prevents the expression of a functional FcRn protein, resulting in a transgenic knockout mouse in which exogenously administered IgG1 exhibits a substantially shorter half-life, as compared to the half-life of exogenously administered IgG1 in a wild-type mouse. The transgenic knockout mouse with a homozygous RcRn disruption is also unable to absorb maternal IgG in the prenatal or neonatal stage of development. Also disclosed is a transgenic knockout mouse comprising a homozygous FcRn disruption and a human FcRn transgene. The transgenic addition of human FcRn results in a substantial increase in the half-life of exogenously administered human IgG1. Methods of using the transgenic knockout mouse, and cells derived from them, are also disclosed.

Abstract: A method of expressing in vivo heart-specific fluorescence in transgenic line of zebrafish is developed, which provides a research model for studying heart-related gene functions and performing gene therapies in the future. The method comprises the following steps. Firstly, a plasmid is constructed. This plasmid construct includes the upstream regulatory region, the exon 1, the intron 1, and the exon 2 of cmlc2 gene, cDNA of GFP, wherein the cmlc2 gene and GFP cDNA form a cassette, and inverted terminal repeats from adeno-associated virus are flanked at both sides of this cassette. The plasmid construct is linearized and microinjected into one-celled zebrafish fertilized eggs. Lastly, the heart-specific fluorescent expressed zebrafish are selected and the germline-transmitting transgenic strain is generated.

Abstract: The present invention provides a Fc?RIIa transgenic non-human animal model for autoimmune disease, particularly arthritis. This invention also provides a method of using this model to screen compounds that can reduce aberrant immune activity including aberrant immune complex formation aberrant immune complex clearance and immune complex induced inflammation. This invention also provides means of using this model to treat or prevent autoimmune disease.

Abstract: The invention provides nucleic acid sequences which regulate expression of a nucleotide sequence of interest. In particular, the invention provides nucleic acid sequences which regulate expression of a nucleotide sequence of interest in an age-related manner and/or in a liver-specific manner. The invention further provides methods of using the regulatory nucleic acid sequences provided herein for age-related and/or liver-specific expression of nucleotides seuqences of interest. The invention also provides host cells and transgenic non-human animals which harbor the regulatory nucleic acid sequences of the invention. The compositions and methods of the invention are useful in regulating expression of a nucleotide sequence of interest in an age-related and/or liver-specific manner.

Abstract: The invention relates to genetically manipulated animals that are deficient in the expression of Caspase-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: Transgenes encoding exogenous proteins are stably integrated into embryonic stem cells and are present in the somatic tissue of transgenic or chimeric birds. The transgenes encode exogenous proteins and are expressed in any of endodermal, ectodermal, mesodermal, or extra embryonic tissue. Tissue specificity is provided by selecting the content of the transgene accordingly. Transgenic birds whose genome is comprised of trangene derived exogenous DNA express exogenous proteins with tissue specificity, and specifically express exogenous proteins in the tubular gland cells of the oviduct to concentrate exogenous proteins in egg white.

Abstract: The invention provides transgenic animals that are heterozygous or homozygous for a nonfunctional allele of BACE-1. These animals show normal development indicating that BACE-1 is not necessary for development and hence is an appropriate therapeutic target. The transgenic animals are useful in various screening assays including identifying inhibitors of other enzymes involved in processing of APP to A? and determining a toxicity profile of inhibitors of BACE-1.

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 or complete contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.

Abstract: Recombination in mammalian somatic cell chromosomes is promoted and marked by a method called mosaic analysis with double marker (MADM). Mouse “knock-in” techniques are used to create pairs of chromosomes in which recombinase target sites are placed at homologous chromosomal locations. The knock-in constructs are engineered so that cellular markers, such as green or red fluorescent protein (GFP or RFP), are only expressed after recombinase-induced recombination. This system provides high-sensitivity detection of recombinase-induced mitotic recombination, even down to the single cell level. When this recombination is induced in a mouse heterozygous for a mutation in a gene distal to the “knock-in” locus on the same chromosome, it results in homozygosity of this mutation in the labeled cells. This allows the analysis in singly-labeled neurons of genes whose pleiotropic effects might otherwise result in early lethality.

Abstract: An object of the present invention is to provide a model mammal for diabetes onset, being useful for elucidating the onset mechanism of diabetes caused by a blockage of signal transduction from insulin, and for the development of a remedy for said diabetes, and to provide a screening method of a remedy for said diabetes. A diabetic-prone transgenic mouse is prepared in a process comprising the steps of: a transgene that contains a Meg1/Grb10 gene, an imprinted gene exhibiting maternal expression, or a human GRB10 gene in the downstream of a chicken ?-actin promoter and in the upstream of a rabbit ?-globin poly A is constructed, and subsequently the transgene is microinjected into a male proneucleus of a mouse fertilized egg; thus obtained egg cell is cultured and then transplanted into an oviduct of a pseudopregnant female mouse; after rearing up the recipient animal, baby mice that have the above-mentioned cDNA are selected from the mice born from the recipient animal.

Abstract: A transgenic animal in which GSK-3? protein is over-expressed is useful as a model for neurodegenerative disease.

Abstract: The invention provides methods for cloning mammals that allow the donor chromosomes or donor cells to be reprogrammed prior to insertion into an enucleated oocyte. The invention also features methods of inserting chromosomes or nuclei into recipient cells.

Abstract: Disclosed are improved methods of treating individuals with Alzheimer's disease (AD) as well as methods to diagnose AD in an individual. Also included are compounds and methods of identifying compounds to treat AD. The present invention also discloses methods for decreasing the phosphorylation of amyloid precursor protein (APP), including inhibiting phosphorylation of amino acid residue tyrosine 668 of APP and for reducing cleavage of APP. The present invention further discloses transgenic (Tg), non-human animals and cells expressing a p25 transgene that are models of neurodegenerative diseases. Embodiments of the present invention are directed to methods wherein the Tg animals and Tg cells of the invention are used to screen for modulators of neurodegenerative disorders. The Tg animals and cells of the present invention are useful for elucidating the mechanisms of neurodegenerative disorders.

Abstract: The present invention relates to a novel animal model for amyloidopathies, especially Alzheimer' disease overexpressing human BACE and human APP London. This novel animal model exhibits several aspects of amyloidopathy. The present invention also relates to a method for producing the double transgenic animals, to cells and cell lines derived from these animals and to a kit comprising these cells. Moreover, a method for the evaluation of the in vivo effects of beta-secretase activity on A-beta peptide generation, amyloidosis, neurodegeneration and AD pathology in these animals is provided.

Abstract: The present invention provides transgenic, non-human animals that include a transgene that encodes a fatty acid desaturase, e.g., stearoyl-CoA desaturase, and methods for producing such animals. The invention further provides an expression cassette that includes a coding region for a desaturase such as stearoyl-CoA desaturase, operably linked to a heterologous, tissue-specific animal cell promoter. The invention further provides methods of producing a food product, such as milk, meat, or eggs, using a subject transgenic non-human animal, as well as food products harvested from a subject transgenic non-human animal.

Abstract: Transgenic non-human mammals over-expressing MHCI in skeletal muscle are provided herein, as are methods of using these transgenic non-human mammals for screening candidate compounds for treating type 2 diabetes, and methods for altering the ratio of MHCI to MHCII in a subject.

Abstract: The present application disclosed a method for preparing a sterile transgenic fish, comprising constructing antisense RNA expression vector of salmon-type gonadotropin-releasing hormone, introducing the recombinant DNA fragment into carp oosperm by microinjection, and screening the sterile transgenic fish by Polymerase Chain Reaction and radioimmunoassay, wherein the expression vector comprising a promoter of carp beta actin (?-actin) gene, a complementary DNA fragment of antisense salmon-type gonadotropin-releasing hormone (sGnRH) gene from carp with 323 bp as a target gene comprising sGnRH decapeptide, the coding region of gonadotropin-releasing hormone associated peptide and 3? non-coding sequence, and 3? flanking sequence of grass carp growth hormone gene as a stop sequence.

Abstract: A system for observing the behaviors of mitochondria during ontogeny and the dynamics of mitochondria in various tissues during pathological development is provided. A pCAGGS expression vector containing green fluorescent protein (GFP) gene and a transgenic animal characterized by expressing GFP specifically in mitochondria are provided.

Abstract: Transgenic non-human animals that express the ?3 subunit of PRKAG are described, as well as methods of using the transgenic non-human animals as models for improving treatment, prevention, or diagnosis of diseases related to energy metabolism, including obesity, dyslipidemia, insulin resistance syndrome, and type 2 diabetes.

Abstract: Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.

Abstract: The present invention provides methods of producing transgenic livestock animals. The methods generally involve first introducing a nucleoprotein made up of nucleic acid and a recombinase into a totipotent or pluripotent cell to produce a recombinant totipotent or pluripotent cell and then growing the recombinant totipotent or pluripotent cell to produce the transgenic livestock animal. The invention further provides kits for use in generating transgenic non-human animals of the invention.

Abstract: A mammalian cell having a mismatch repair-deficient phenotype is provided, where one or both alleles of a gene essential for mismatch repair, such as an Msh gene, are inactivated. Using this cell in a gene knock-out methodology advantageously allows efficient homologous recombination, even when the DNA sequences of the donor and recipient sequences diverge by significantly more than 0.6%.

Abstract: The present invention is directed toward a transgenic non-human animal and uses thereof, wherein each of the cells of the animal contain a transgene comprising a nucleic acid sequence encoding CD200.

Abstract: A transgenic mouse whose genome comprises a transcriptional control region operably linked to a cDNA encoding calreticulin (CRT) is described.

Abstract: The present invention relates to the use of leukemia inhibitory factor (LIF) in the isolation and propagation of embryonic stem cells in vitro.

Abstract: Sustained cultures of avian embryonic stem cells are provided. Injection of avian embryonic stem cells into recipient embryos yields chimeras with a significant contribution from the embryonic stem cell phenotype. Transgene encoding exogenous proteins are stably integrated in the embryonic stem cells and are present in the somatic tissue of the resulting chimeras. The transgenes may encode exogenous proteins expressed in endodermal, ectodermal, mesodermal, or extra embryonic tissue. Breeding the resulting chimera yields transgenic birds whose genome is comprised of exogenous DNA.

Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Utilizing assays based upon the nucleic acid sequences disclosed herein (as well as mutant forms thereof), numerous molecules may be identified which modulate the immune system.

Abstract: The invention relates to a method for producing a protein of interest comprising transforming a target insect with a non-viral expression system that expresses the protein in the insect larvae, breeding the insect to produce larvae, culturing the larvae and isolating the protein from the larvae.

Abstract: The present invention relates generally to the field of generating genetically modified C57 mice. More particularly, the present invention pertains to 1) blastocyst-derived mouse embryonic stem cell (ES) cell lines including, but not limited to, the IC1, IC2, IAC1, IAC2, IAC3, IAC4, IAC5, IAC6, IAC7 or IAC8 ES cell line, 2) to efficient methods of making genetically modified C57 mice by introducing the modified C57 ES cells into the mouse blastocysts of either the same mouse strain and/or color of albino C57 strain, or other C57 strain, to generate genetically modified novel, useful and hereto unknown models of C57 mice, and to methods for identifying the chimerism of chimeras which can be not known by coat color.

Abstract: The present invention discloses a method for expressing multiple recombinant proteins in transgenic non-human mammalian milk, characterized in which human clotting factor IX gene and porcine lactoferrin gene are transferred into the mammal by gene injection and embryonic implantation to obtain expression in the milk of transgenic mammal and its filial generation. The method of this invention can maintain the stable expression of multiple recombinant proteins in the transgenic mammal during lactation and stable expression amount proximate to that of the first generation in the offsprings of the transgenic non-human mammal.

Abstract: An improved method of nuclear transfer employing long-term cultured somatic cells as the donor cells and enucleated oocytes as the recipient cells to produce dividing cybrids. Such cybrids are useful for developing viable animals clones when nurtured in a suitable host environment.

Abstract: A method of identifying a genotype of a transgenic mouse and reducing the variability of a transagene expression in the transgenic mouse comprises the step of introducing into a mouse (a) a transgene expression cassette, (b) a coat color expression cassette and (c) an insulator positioned at 5? or 3? end of the transgene expression cassette.

Abstract: A transgenic rodent or its offspring which carries DNA having an exogenous caspase 1 gene integrated thereinto in such a manner as to express the gene specifically to the skin. The transgenic rodent of the present invention spontaneously develops atopic dermatitis in the absence of any specific pathogenic microorganism and is useful as a disease model animal. The transgenic rodent of the present invention is useful for developing preventive and/or therapeutic drugs for atopic dermatitis based on natural immunity and to clarify the onset mechanism of atopic diseases.

Abstract: The present invention is directed to a vector and its use to generate genetically modified animals and cells. One aspect of this invention involves a vector that comprises a sperm cell and one or more polynucleotide molecules bound to a sperm cell through one or more non-liposome based linkers. In a preferred embodiment of this invention, the linker is a protein or polypeptide, preferably sperm specific such as an antibody that binds with the external surface of the sperm cell. In another aspect of the present invention, genetically modified cells or animals are derived from the fertilization of an animal egg cell with the vector described. In one preferred embodiment, genetic modification occurs with the polynucleotide molecule integrating, wholly or partially, into the cell or animal's genome. Another aspect of the present invention includes cells, such as sperm cells or egg cells, and cell lines that are derived from these genetically modified animals or their descendants.