Abstract: The present invention provides methods of identifying candidate agents for treating excitotoxicity-related disorders. The present invention further provides methods for treating excitotoxicity-related disorders.

Abstract: The present invention provides an expression vector, containing expressibly (a) a polynucleotide encoding a fusion protein of a mutant of a repressor protein, which binds to an antibiotic, and a target protein, and (b) a polynucleotide encoding a protein controlling the transcription of the polynucleotide in (a), the transcription of the polynucleotide in (a) and the degradation of said fusion protein, which is the expression product of the polynucleotide in (a), being controlled inside a cell by the presence or absence of an antibiotic inside the cell.

Abstract: A transgenic mouse expressing JSRV Env transgene that is operably linked to a surfactant protein C promoter (SPCp) is disclosed. The transgenic mouse is prone to developing a lung tumor and serves as an animal model for human lung carcinoma.

Abstract: A mammalian C-type lectin receptor type is identified which is shown to bind IgG antibodies or Fc fragments, thus inducing WIG-related reversal of inflammation associated with various immune disorders. The identification of a DC-SIGN receptor type which interacts with IgG to promote a biological response reducing inflammation associated with immune disorders provides for methods of screening and selecting compounds which may be useful in treating various immune disorders by acting to modulate a DC-SIGN(+) cell to signal a second effector macrophage, causing an increase in expression of the Fc?RIIB receptor and in turn inhibiting a cellular-mediated inflammatory response.

Abstract: The present invention relates to a method for identifying an inhibitor of the aggregation of amyloid-? peptide (A?), comprising the steps of a) contacting at least one A?-peptide and/or the nitrated forms thereof with at least one candidate inhibitor that potentially specifically binds to a region in said A?-peptide capable of being nitrated, and b) detecting said inhibitor specifically binding to said region in said A?-peptide through detecting a lack of or a reduced aggregation of said at least one A?-peptide. The present invention is further directed at improved methods for treating neuronal degradation and particularly Alzheimer's disease, based on said inhibitor. The present invention is further directed at methods for diagnosing the aggregation of A?-peptide in the context of neuronal degradation and particularly Alzheimer's disease.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO227, PRO233, PRO238, PRO1328, PRO4342, PRO7423, PRO10096, PRO21384, PRO353 or PRO1885 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.

Abstract: The present invention relates to the field of neurological disorders and more particularly to the field of neuropsychiatric disorders. The invention provides non-human, transgenic animal models for brain disorders such as schizophrenia, bipolar disorders, compulsive disorders, addictive disorders and the like. The animals also have applications in the field of GABA neuro-transmission and other disorders in which GABA-dependent gene regulation has a role.

Abstract: The instant invention relates to the use of 24-hydroxylated vitamin D compounds as therapeutics in mammalian bone fracture repair. In addition, the instant invention relates to novel 24-hydroxylated vitamin D compound receptors which can be employed in the development of compounds capable of facilitating fracture repair in animals. The instant invention also relates to nucleic acids encoding such receptors as well as vectors, host cells, transgenic animals comprising such nucleic acids and screening assays employing such receptors.

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: The present invention relates to the field of endothelial haematopoietic transition (EHT) and epithelial-mesenchymal transition (EMT) and more particularly relates to the use of fish embryo or larva as a model for the study of EHT and EMT.

Abstract: The present invention provides a transgenic animal model of Alzheimer's Disease designated TgCRND8 as well as a method for making such model, which allows for the characterization of the etiology of the disease as well as for provide a system for the development and testing of potential treatments.

Abstract: A method is described to identify secreted proteins identified with stages of malignancy of cancer. The proteins are initially identified by trapping them with a fluorescent protein containing vector that can insert in any gene. The secreted proteins are initially identified by their fluorescence. Secreted proteins identifying tumors with specific degrees of malignancy are isolated to determine if they can serve as markers of cancer progression.

Abstract: The invention relates to the field of longevity enhancement. More particularly, the invention provides compositions and methods relating to CRTC modulation. In certain embodiments, the invention provides compositions and methods for enhancing longevity in an organism by inhibiting CRTC activity, such as, for example, inhibiting CRTC expression or cellular localization in the organism.

Abstract: The invention provides methods of preventing or treating drug addiction, or ameliorating the craving for an addictive drug, as well as compounds, peptides, and pharmaceutical compositions that may be used to prevent or treat drug addiction or ameliorate the craving for an addictive drug. The invention also provides methods for identifying agents that may be used to prevent or treat drug addiction, or ameliorate the craving for an addictive drug.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO224, PRO9783, PRO1108, PRO34000, PRO240, PRO943, hu A33, PRO230, PRO178, PRO1199, PRO4333, PRO1336, PRO19598, PRO1083, hu TRPM2 or PRO1801 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.

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

Abstract: The present invention is directed to the production, breeding and use of transgenic non-human animals such as mice in which specific genes or portions of genes have been replaced by homologues from another animal to make the physiology of the animals so modified more like that of the other animal with respect to drug pharmacokinetics and metabolism. The invention also extends to the use of the genetically modified non-human animals of the invention for pharmacological and/or toxicological studies.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO226, PRO257, PRO268, PRO290, PRO36006, PRO363, PRO365, PRO382, PRO444, PRO705, PRO1071, PRO1125, PRO1134, PRO1155, PRO1281, PRO1343, PRO1379, PRO1380, PRO1387, PRO1419, PRO1433, PRO1474, PRO1550, PRO1571, PRO1572, PRO1759, PRO1904, PRO35193, PRO4341, PRO4348, PRO4369, PRO4381, PRO4407, PRO4425, PRO4985, PRO4989, PRO5737, PRO5800, PRO5993, PRO6017, PRO7174, PRO9744, PRO9821, PRO9852, PRO9873, PRO10196, PRO34778, PRO20233, PRO21956, PRO57290, PRO38465, PRO38683 or PRO85161 genes.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with MD. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study MD development and methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with MD.

Abstract: The present invention provides, in some aspects, methods for identifying agents useful in treating disorders or conditions associated with cognitive deficits. In some aspects, the invention provides methods for detecting a cognitive deficit in a subject.

Abstract: The present invention relates to the use of AxI as a biomarker for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject. More specifically, the invention relates to various methods for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject by measuring AxI expression and/or activity.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in ADME and toxicology. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence involved in ADME and toxicology and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences involved in ADME and toxicology.

Abstract: Animal models and methods wherein homoplasmic and heteroplasmic mtDNA mutation(s) are induced in an animal (e.g., a mouse) to cause or facilitate the development of a disorder (e.g., disease, malformation, defect, abnormality or other disorder). In at least some embodiments, the mtDNA mutation(s) will cause or facilitate the development of an age-related disorder, such as a cardiac disease, cardiomyopathy, muscle disease, cancer, abnormaly in tissues of high cellular turnover, heart dysfunction, graying of hair, alopecia, auditory function loss, cochlear degeneration, immune cell loss, anemia, male germ cell loss leading to lack of sperm and infertility, skeletal muscle mass loss (sarcopenia), neurodegeneration, increased presence of apoptotic markers, and loss of bone mass.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in altered nervous system function. In one aspect, the altered function results in pain in the mammal. In another aspect, the nervous system dysfunction results in prolonged hyperalgesia, allo dynia, and loss of sensory function. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of altered nervous system function mediated pain and methods of their use. In another aspect, the genetically modified rats, as well as the descendants and ancestors of such animals, are animal models of nervous system dysfunction resulting in prolonged hyperalgesia, allodynia, and loss of sensory function and methods of their use.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: The invention relates to the treatment or prevention of an inflammatory skin disease, disorder or condition, by modulating a protein that is normally regulated by caspase-8 in the skin or by increasing caspase-8 activity or level in the skin. Another aspect of the invention relates to methods for diagnosing an inflammatory skin disease, disorder or condition or a predisposition to develop said disease disorder or condition in an individual. Further aspects of the invention relate to methods for identifying target proteins involved in the course or pathology of an inflammatory skin disease, disorder or condition and to methods of screening a candidate compound for treating said disease, disorder or condition. In particular, the invention relates to inflammatory skin diseases such as atopic dermatitis and psoriasis.

Abstract: Embodiments of the present disclosure include double-fusion human embryonic stem cells, methods of imaging double-fusion human embryonic stem cells, double-fusion polynucleotides, double-fusion proteins, triple-fusion human embryonic stem cells, methods of imaging triple-fusion human embryonic stem cells, triple-fusion polynucleotides, triple-fusion proteins, methods of monitoring the progression of human embryonic stem cells, methods of making isolated double-fusion human embryonic stem cells, methods of making isolated triple-fusion human embryonic stem cells, and the like.

Abstract: A trifusion reporter plasmid is described that comprises a plasmid operably coupled to a mammalian FGF1B promoter that is operably coupled to a bioluminescence gene fused to a fluorescence gene fused to a nuclear medical imaging gene. The new reporter allows in vivo or ex vivo detection of gene expression in three different ways, in addition to traditional in vitro detection methods. Transgenic animals containing this new trifusion reporter and uses of same are described.

Abstract: A system including: (i) a methodology for targeted cellular ablation in zebrafish; (ii) a methodology for regional cellular ablation in zebrafish. These methodologies are used to identify genetic components that regulate cellular regeneration and to identify drug compounds that influence cellular regeneration for the purpose of developing therapies for degenerative conditions. Transgenic zebrafish disclosed herein contain transgenic constructs composed of: (i) cell and/or tissue-type specific regulatory elements (e.g.

Abstract: The invention relates to nematodes as model organisms for the investigation of neurodegenerative diseases, in particular, Parkinsons disease, uses and methods for the discovery of substances and genes which can be used in the treatment of the above disease states and identification of a nematode gene, From C elegans, which is homologous to the human parkin gene associated with Parkinsons disease. The invention further relates to those nematodes which contain an aberrant or missing expression of at least one gene, preferably a parkin gene and/or a ?-synucleine gene, which is connected with Parkinsons disease. According to the invention, the above organisms can be used for the identification and characterization of medicaments for the treatment of said disease states.

Abstract: The present invention belongs to the field of pharmaceutical industry and specifies a method for testing extraneous agents in a composition comprising at least one active agent, comprising the steps of: a) contacting an antibody, which had been raised against an expression product of a polynucleotide construct comprising a sequence encoding at least a part of the active agent, with the composition comprising at least one active agent, wherein the antibody binds to the active agent, and b) determining the presence or absence of extraneous agents in the composition subsequent to step a). Furthermore, the invention specifies a process for producing a pharmaceutical composition by carrying out said method, to the use of a polynucleotide construct for testing the presence or absence of the active agent or of any extraneous or infectious agent in a composition to be tested.

Abstract: The invention related to the use of high-density loss of heterozygosity (LOH) mapping in lung adenocarcinoma to identify intragenic LOH and driver mutations in different domains of ALK resulted in enhanced tumor growth in xenografted mouse. Mutant (H694R and E1384K) ALKs showed activation of Y1604 ALK and downstream AKT, STAT3 and ERK signaling pathways. Increases of oncogenic signalings resulted in enhanced cell proliferation, colony-formation, cell-migration and tumor-growth in xenografted mouse. Western blot and immunohistochemistry analysis using antibody against phospho-Y1604 ALK on 11 lung cancer cell-lines and 263 cancer specimens indicated ALK activation in all lung cancers regardless of tumor stages. Treating mutant-bearing mice with ALK inhibitor WHI-P 154 resulted in tumor shrinkage, metastasis suppression, and improved survival. Hyperphosphorylation of Y1604 ALK occurred early and continuously throughout tumor progression and could be used as a biomarker to detect lung cancer.

Abstract: The present invention provides an agent that modulates physiological condition of pests, wherein the agent has an ability to modulate the activity of an insect voltage-gated potassium channel; a method for assaying pesticidal activity of a test substance, which comprises measuring the activity of a voltage-gated potassium channel in a reaction system in which the voltage-gated potassium channel contacts with a test substance, and so on.

Abstract: The invention relates to the field of longevity enhancement. More particularly, the invention provides compositions and methods relating to modulation of mitochondrial function. In certain embodiments, the invention provides methods and related compositions for the enhancement of longevity in an animal, comprising inhibition of one or more electron transport chain components, such as cco-1 and homologs thereof, in a tissue-specific manner in the animal.

Abstract: Provided are a DNA fragment, a pharmaceutical composition, and the like, which can simplify the period of creating knockout animals. The DNA fragment includes: a detection sequence that codes for a detection marker other than drug resistance (preferably a visually-detectable marker); a resistance sequence that codes for a resistance marker for a drug that inhibits the proliferation of one or more species of at least prokaryotic organisms; a promoter sequence that is located upstream of the resistance sequence and functions in prokaryotic organisms; and a regulatory sequence that is located upstream of all of the above sequences and, only when inserted into a target region of the genome of at least one species of eukaryotic organism, induces the expression of a sequence located downstream. The detection sequence and the resistance sequence are arranged so as to be capable of action.

Abstract: A mouse model is provided which is directed to mice bred to have a disruption in the TGF-? signaling pathways which causes tumorigenesis in the liver and gut of the developing mice. The mice models of the invention include those mice whose genome include at least one mutant allele of a protein involved in the TGF-? signaling pathway, such as the elf protein or to the Smad proteins, and such models are advantageous in that they allow the study of tumor suppression and development in the liver and gut and can thus be used to study, assess and treat a variety of forms of hepatocellular and gastrointestinal cancer. Use of the Elf and Smad proteins and antibodies thereto in the diagnosis and treatment of liver and gut tumors is also provided.

Abstract: A nucleic acid expression construct which encodes a fusion protein includes a reporter protein and a protein with a wild-type destruction signal. A sequence encoding the fusion protein is operably linked to a non-endogenous promoter. The fusion protein localizes during a cell cycle progression to subcellular structures selected from a cell cortex, a contractile ring, and a midbody.

Abstract: An isolated polynucleotide encoding a modified luciferase polypeptide and novel coelenterazine-based substrates. The OgLuc variant polypeptide has at least 60% amino acid sequence identity to SEQ ID NO: 1 and at least one amino acid substitution at a position corresponding to an amino acid in SEQ ID NO: 1. The OgLuc variant polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the corresponding polypeptide of the wild-type Oplophorus luciferase.

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: An epilepsy model animal (CHRNA4:S284L) developing spontaneous epileptic seizure during sleep, which is a nonhuman animal established by ontogenesis of a totipotent cell into which a polynucleotide encoding nonhuman mutant CHRNA4 is introduced and having said polynucleotide in its somatic chromosome, or a progeny of the nonhuman animal, wherein said nonhuman mutant CHRNA4 has the corresponding mutation of human mutant CHRNA4 in which the 284th Ser of SEQ ID NO: 1 is substituted by Leu. The epilepsy model animal has gene abnormality homologous to human chromosomal dominant nocturnal frontal lobe epilepsy and a symptom (epileptic seizure during sleep) the same as that of human autosomal dominant nocturnal frontal lobe epilepsy.

Abstract: The invention relates to the use of fetal tissues to generate a tissue model in a non-human animal. The tissue model comprises target tissues allowed to progress through development in vivo in a non-human host in order to obtain tissues having a mature phenotype that can be used to assess toxicity and/or efficacy of an agent.

Abstract: Transgenic animals containing a nucleic acid sequence encoding TCL1 operably linked to transcriptional control sequences directing expression to B cells are described. Such transgenic animals provide a useful animal model system for human B cell chronic lymphocytic leukemia.

Abstract: Inhibitors of luciferase enzymes are disclosed and find use in multiplexed assays using multiple luciferases and multiple inhibitors, in both in vitro and in vivo embodiments.

Abstract: The present invention relates to a non-human transgenic animal whose genome comprises a stably integrated transgenic nucleotide sequence encoding Lysine-specific Demethylase 1 (LSD1) operably linked to a promoter. The invention further concerns methods for generating the non-human animal and its use as a cancer model.

Abstract: Porcine animals, tissue and organs as well as cells and cell lines derived from such animals are provided that lack functional endogenous immunoglobulin loci and are deficient in immunoglobulin expression and B-cells. These animals are useful as model systems for research and for development of new pharmaceutical and biological agents. In addition, methods are provided to prepare such animals.

Abstract: The present invention is directed to the production, breeding and use of transgenic non-human animals such as mice in which specific genes or portions of genes have been replaced by homologues from another animal to make the physiology of the animals so modified more like that of the other animal with respect to drug pharmacokinetics and metabolism. The invention also extends to the use of the genetically modified non-human animals of the invention for pharmacological and/or toxicological studies.

Abstract: This invention relates transgenic animals that overexpress TL1A in a tissue specific manner to model inflammatory bowel disease (IBM such as colitis, Crohn's disease and ulcerative colitis, fibrosis, and related inflammatory diseases and conditions. TL1A transgenic animals constitutively express both TL1A and GFP in lymphoid and myeloid cell lineages, allowing convenient identification and sorting of immune cells involved in IBD disease progression, such as T-cells, antigen presenting cells (APC), and dendritic cells (DC). TL1A transgenic animals may be induced to exhibit gross fibrosis, or isolated cells may be implanted into immunodeficient mice to establish colitis.

Abstract: The invention features therapeutic compositions comprising agents useful for the treatment or prevention of pruritis, and methods useful for identifying such agents.

Abstract: A transgenic non-human animal for overexpressing isoQC, comprising cells containing a DNA transgene encoding human isoQC, characterized in that said human isoQC comprises the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 1 or a fragment or derivative of the amino acid sequence of SEQ ID NO: 1. Additionally disclosed is a method of screening for biologically active agents that inhibit or promote isoQC.

Abstract: The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.