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 disclosure provides methods and compositions useful for screening inhibitors of aggregation mediated proteotoxicity. The disclosure provides transgenic animals and cell useful for such screening. Also provided are compounds useful for inhibiting aggregation mediated proteotoxicity in a subject.

Abstract: The present invention provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase II? promoter operatively linked to a gene of interest. The region of a calcium-calmodulin dependent kinase II? promoter may comprise an 8.5 kilobase nucleic acid sequence which corresponds to the nucleic acid sequence of ATCC Accession No.: ______, designated pMM281. The present invention also provides a human cell line which has been stably transformed by a recombinant nucleic acid molecule comprising a gene of interest operatively linked to a nucleic acid encoding a calcium-calmodulin dependent kinase II? promoter region which has a nucleotide sequence corresponding to the sequence of ATCC Accession No. ______, designated pMM281. The present invention also provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes a gene of interest under the control of a CaMKII? promoter (ATCC Accession No.

Abstract: This invention provides methods, compositions and kits for rapid determination of the delivery of exogenous agents both in vitro and in vivo, including without limitation siRNA, microRNA, a ribozyme or an antisence molecule, any of which may target, bind to, or inactivate the mRNA of the gene of interest expressed in the cells. The methods, compositions and kits utilize a promoter-reporter construct whereby successful non-viral nucleic acid delivery leads to an up-regulation of reporter signals thus providing a quantitative, sensitive and rapid means of detection, validation and monitoring.

Abstract: A transgenic animal such as a transgenic snake or other reptile that expresses a heterologous expression product is described, along with methods of making the same. In general, the animal comprises cells containing a sequence encoding the heterologous expression product. The sequence encoding the heterologous expression product is integrated into the genome of the animal (e.g., in some or all cells thereof, and in some embodiments into germ cells thereof). The sequence encoding the heterologous expression product is, in general, operatively associated with an expression sequence or promoter. The animals are useful for, among other things, testing of repellents, testing of toxicological compounds, as teaching aids, for venom production, etc.

Abstract: The present invention provides methods for treating fragile X syndrome and/or other neurodevelopmental disorders by administering p21-activated kinase (PAK) modulators to a patient suffering from, susceptible to, and/or exhibiting one or more symptoms of FXS and/or other neurodevelopmental disorders. The present invention provides PAK modulators and pharmaceutical compositions comprising PAK modulators. The present invention further provides methods for identifying and/or characterizing PAK modulators.

Abstract: The present invention relates to the discovery, identification and characterization of a receptor protein, referred to herein as T1R3, which is expressed in taste receptor cells and associated with the perception of bitter and sweet taste. The invention encompasses transgenic animals and cells that do not express functional T1R3 protein, particularly knock-out animals and cells, and transgenic animals and cells that express a non-native T1R3 protein. Experimental model systems based on these animals and cells can be used to study T1R3-mediated taste transduction and responses of the components of the T1R3 signal transduction pathway to various tastants, furthering our understanding of the molecular biology and biochemistry of taste. Such model systems would also be useful for screening for novel tastants and taste modulators, such as enhancers of desirable flavors, and blockers of undesirable flavors.

Abstract: The instant invention is based, at least in part, on the discovery that T-bet maintains host commensal relationships in the gastrointestinal tract. Accordingly, this invention provides methods of treating and/or preventing ulcerative colitis, and/or colon cancer, and/or preventing colonization of a subject's gastrointestinal tract with commensal bacteria that promote ulcerative colitis as well as methods of identifying agents that treat and prevent the same.

Abstract: The invention provides genetically altered fish of the family Cyprinidae, or genus Danio, including zebrafish (Danio rerio) and host cells from these animals, where the fish have been genetically altered to lack or have a modified gene related to lipid metabolism, for example, an ApoE, ApoAI and/or LDL-R gene. In another aspect, the invention is directed to drug design or discovery using the animal or cell models of the invention and/or wild type zebrafish, and by administering an altered diet and/or environment to the animal of invention. The invention also provides methods for screening for a compound capable of ameliorating or preventing or reversing: atherosclerosis; hyperlipidemia; lipoprotein oxidation; the accumulation of lipid in a blood vessel wall; vascular inflammation associated with lipid accumulation in a blood vessel wall; acute atherosclerosis-associated events; heart attack; stroke.

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: 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: The present invention provides a hairless transgenic nonhuman animal used in the development of a therapy for dermatitis such as human atopic dermatitis and drug discovery. Specifically, the present invention provides a transgenic nonhuman animal, into which recombinant DNA comprising a heparin-binding EGF gene and a type 2 keratin gene promoter for regulating expression of the above gene has been introduced.

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 PRO1105, PRO1279 or PRO1783 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 methodologies of the present invention demonstrate that a critical balance between pro- and anti-amyloidogenic molecules exists that regulates amyloid formation and cell death in Alzheimer's disease and Parkinson's disease. ?-Synuclein, the non-amyloidogenic homologue of ?-synuclein, is a negative modulator of ?-synuclein and A? aggregation, having neuroprotective properties against ?-synuclein and A? neurotoxicity and that ?-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that ?-synuclein blocks A? aggregation either by direct inhibition of A? amyloidogenesis or indirectly via either ?-synuclein or its 35 a.a. NAC region, inferring neuroprotective characteristics within the effected cells.

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: A method for screening for or diagnosis or prognosis of a neurological disorder associated with de-regulated glutamate signalling in a subject, for determining the stage or severity of such a neurological disorder in a subject, for identifying a subject at risk of developing such a neurological disorder, or for monitoring the effect of therapy administered to a subject having such a neurological disorder, said method comprising: (a) analyzing a test sample of body fluid or tissue from the subject said sample comprising at least one Protein Isoform selected from the following Protein Isoform Families: PIF-1, PIF-2, and PIF-3 in a detectable amount; and (b) comparing the abundance of said Protein Isoform(s) in the test sample or the abundance of said Protein Isoform(s) relative to another Protein Isoform with the abundance or relative abundance of said Protein Isoform(s) in a test sample from one or more persons free from neurological disorder, or with a previously determined reference range for that Protein

Abstract: A modular platform is provided for rapid preparation of various water-soluble prosthetic groups capable to efficiently introduce 18F into proteins with 18F labelling reagents.

Abstract: Methods of treating metabolic stress disorders are disclosed that include administering to a subject a therapeutically effective amount of a composition that specifically inhibits the expression or activity of a mixed lineage kinase (MLK). Also disclosed are methods of identifying candidate compounds for treatment of metabolic stress disorders and methods of diagnosing metabolic stress disorders.

Abstract: The present invention relates to a novel target for identifying and/or screening antitumor and/or antiangiogenesis agents using the rcl encoded deoxynucleoside 5?monophosphate N-glycosidase.

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 is in the field of identification and characterization of novel insecticidal target sites and, in particular, relates to host cells, assays and antibodies thereto.

Abstract: This invention provides the identification of a truncation polymorphism of the mdr1 gene that is linked to ivermectin sensitivity in subjects, such as collies. Also provided are methods for detecting drug transport sensitivity in a subject, and animal models and in vitro cell systems using cells from animals having an mdr1 truncation.

Abstract: It is intended to provide a simple normal-tension glaucoma model capable of spontaneously, age-dependently and surly developing conditions similar to symptoms of normal-tension glaucoma which occurs more frequently in elder people, and a method of evaluating therapeutic effect on normal-tension glaucoma whereby a drug useful in treating and diagnosing can be conveniently screened by using the normal-tension glaucoma model. A normal-tension glaucoma model comprising a nonhuman mammal, which is deficient in a transcriptional regulator NF-?Bp50 and thus spontaneously develops the normal-tension glaucoma symptom age-relatedly, an organ or a tissue thereof or cells collected from any of the same.

Abstract: A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel ? subunit, wherein said promoter construct directs expression of the epithelial sodium channel ? subunit in lung epithelial cells of said animal, and wherein said transgenic mammal has increased lung mucus retention as compared to the corresponding wild-type mammal. The animal is useful in screening compounds for activity in treating lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

Abstract: The present invention relates to a novel class of gene trap vector (enhanced gene trap vectors, eGTV) for efficiently identifying silent or weakly expressed target genes in mammalian genomes, methods of their production and methods for identifying and mutating target genes by using the enhanced gene trap vectors. The gene trap vectors of the present invention can also be used for inducing the expression of silent genes and enhancing the expression of weakly expressed genes. The use of the enhanced gene trap vectors for creating transgenic organisms to identify gene function and to validate pharmaceutical compounds prior to clinical applications is a further aspect of the present invention.

Abstract: To clarify histamine receptor H3 protein function in vivo, the present inventors constructed a nonhuman higher animal in which the expression of a histamine receptor H3 gene was artificially inhibited. As a result, the present inventors found that this nonhuman higher animal showed increased body weight, food intake, blood insulin level, or blood leptin level compared with a control. Thus, the present inventors found that abnormalities in the histamine receptor H3 protein relate to diseases characterized by changes in body weight or food intake, and this has made it possible to screen drugs for treatment or prevention of these diseases, and to examine these diseases.

Abstract: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided. Methods of screening an agent for an activity in the brain or central nervous system in zebrafish are provided. The invention further provides high throughput methods of screening agents in multi-well plates.

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: The invention provides, among other things, methods for performing RNA interference in stem cells and methods for using the stem cells in vivo.

Abstract: The present invention provides transgenic animal models of Parkinson's disease. More specifically, the present invention provides a transgenic rodent animal containing a nucleic acid molecule which encodes a mutant human LRRK2 protein. The transgenic animal of the present invention recapitulates cardinal Parkinson's disease symptoms and characteristics. The present invention also provides methods of screening for a therapeutic agent useful for treating Parkinson's disease by utilizing such transgenic rodent animal.

Abstract: The present invention is a new type of Glycine N-methyltransferase (GNMT) knockout mice model. This model can be applied to screen drug, test of treatment and search for diagnostic marker of hepatocellular carcinoma (HCC), glycogen storage disease, liver dysplasia, fatty liver and other liver disease.

Abstract: This invention is in the field of neurology. Specifically, the invention relates to the discovery and characterization of molecular components that play a role in neuronal demyelination or remyelination. In addition, the invention relates to the generation of an animal model that exhibits hypomyelination. The compositions and methods embodied in the present invention are particularly useful for drug screening and/or treatment of demyelination disorders.

Abstract: The invention relates to modelling diseases, to screening for compounds that modulate such diseases and to as-saying drug metabolism and toxicity in non-human transgenic animals, by a novel technique developed by the inventors known as “somatotransgenic bioimaging”.

Abstract: Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type (WT1) human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either WT1 human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of WT1 LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of WT1 LRRK2. Treatment with L-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase (TH)-positive neurons.

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: Provided herein are novel nucleic acid sequences, vectors comprising such nucleic acid sequences, host cells comprising such vectors, and transgenic animals comprising such nucleic acid sequences, and related molecules and methods relating thereto. Such novel nucleic acid sequences, vectors comprising such nucleic acid sequences, host cells comprising such vectors, and transgenic animals comprising such nucleic acid sequences, and related molecules and methods provide conditional overexpression of genes, such as myostatin, and transgenic animals conditionally overexpression genes, such as myostatin.

Abstract: The present invention relates to the development of a pharmacological non-human animal model that associates memory loss to histopathological features found in the brain of a subject having Alzheimer's Disease. In one embodiment, a four-week continuous infusion of a Fe2+, A?42 and buthionine sulfoximine (FAB) solution in the left ventricle of young adult Long-Evans rats induced memory impairment accompanied by increased hyperphosphorylated Tau protein levels in cerebrospinal fluid. Brains from treated animals displayed neuritic plaques, tangles, neuronal loss, astrogliosis and microgliosis in hippocampus and cortex. The present invention may be utilized in evaluating preventive, therapeutic and diagnostic means for neurologic diseases.

Abstract: A novel method of identifying and obtaining molecules interacting with neurodegenerative, neurological or neuropsychiatric disorder-associated proteins is provided, which is suitable for drug screening and drug development. Furthermore, drugs and drug targets for the therapeutic intervention of neurodegenerative, neurological or neuropsychiatric disorders, in particular Alzheimer's disease are described.

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: The present invention provides a non-human model mammal of Alzheimer's disease (AD) containing chimeric amyloid precursor protein (APP) gene capable of producing human amyloid ? peptide (A?) or a living part thereof, characterized in that A?42/A?40 ratio at 8-weeks-old is about 7-fold or more (about 140-fold or more in homozygote) higher compared to that of a corresponding wild-type mammal. Moreover, the present invention provides the mammal or a living part thereof, further characterized in that the level of APP expression is not significantly different compared to the corresponding wild-type mammal, and a screening method for a prophylactic and/or therapeutic drug for AD, a biomarker in biological fluids and molecular imaging of amyloid deposition or other pathological changes in the brain for an early diagnosis of AD using the mammal or a living part thereof.

Abstract: A nephropathy-associated gene which encodes a transcription repressor; and a nonhuman transgenic animal suffering from nephropathy which is constructed by transferring the above gene and allows the observation of increases in urinary volume, urinary albumin and urinary NAG, pyelectasis, enlargement in kidney tubule and glomerular swelling at the early stage and the following sclerosis.

Abstract: Methods and compositions for modulating carbohydrate metabolism in a host are provided. In the subject methods, diacylglycerol acyltransferase (DGAT) activity (specifically DGAT1 activity) is modulated, e.g., reduced or enhanced, to achieve a desired insulin and/or leptin sensitivity, thereby modulating carbohydrate metabolism, e.g., increasing or decreasing blood glucose levels, glucose uptake into cells and assimilation into glycogen. Also provided are pharmaceutical compositions for practicing the subject methods. The subject methods and compositions find use in a variety of applications, including the treatment of hosts suffering conditions associated with abnormal carbohydrate metabolism, such as obesity or diabetes.

Abstract: The present invention relates to a system of multi-stage stem cell carcinogenesis and a method of generating such multi-stage stem cell carcinogenesis system. Various stages of cancer stem cells can be generated from normal stem cells via mutagenesis. The system of the present invention enables monitoring changes in the ability of cells to transition from one stage of carcinogenesis to another and to identify genetic pathways and molecules that influence carcinogenesis. The present invention also enables a high-throughput and nonbiased screening for targets that preferentially affect cancer stem cells relative to non-cancer stem cells or their derivatives during stem cell carcinogenesis, thus is useful in developing anti-cancer therapeutics.

Abstract: The present invention generally relates to humanized VEGF and non-human transgenic animals expressing it. The transgenic animals are also useful to study VEGF-related therapies.

Abstract: The present invention refers to non-human transgenic mammals, preferably rodents, or mice, which comprise a mutation in the gene encoding for the cardiac ryanodine receptor (RyR2). Transgenic animals carrying the amino acid change R4496C in the RyR2 protein show a phenotype similar to that of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) (OMIM: 604772). Further provided are methods for using these animals as in vivo model of Catecholaminergic Polymorphic Ventricular Tachycardia and RyR2 dependent arrhythmias, in drug screening and for understanding the molecular basis of RyR2 dependent arrhythmias.

Abstract: The present invention provides ZPA polypeptides, antibodies, nucleic acid molecules, antagonists, agonists, potentiators and compositions relating to ZPA polypeptides, and methods of identifying, making and using the same, that are useful for treating and preventing diseases and for medical diagnosis and research. The present invention also provides model systems for the intrinsic apoptotic pathway.

Abstract: The present invention relates to identification of cellular components, genotypes and gene expression profiles associated with mood disorders. In some embodiments, the present invention relates to the correlation between ribosomal protein S6 (RPS6) and depression and/or anxiety. Embodiments of the present invention further relate to regulation of the activity of RPS6, e.g., by p90 Ribosomal S6 protein kinase. Embodiments of the present invention provide methods and compositions for, e.g., diagnosing, treating, and monitoring depression and/or anxiety, or risk thereof, and for selecting, monitoring, and tailoring treatments for depression and/or anxiety.

Abstract: The present invention relates to compositions and methods useful for detecting and/or measuring, e.g., intracellular signaling in vivo. More particularly, compositions and methods are provided, which include transgenic animals, that are useful in mapping and examining, e.g., calcium fluctuations in vivo between and within populations of cells in real time. Methods for screening for candidate compounds that effect, e.g., intracellular calcium signaling are also provided.

Abstract: The invention relates to compositions comprising, and methods utilizing PBK1 protein and DNA, including a method of detecting type 1 diabetes; a mammalian pancreas-derived cell comprising a recombinant nucleic acid encoding a PBK1 protein; a method of identifying a PBK1 modulator; a pharmaceutical composition for treatment of type 2 diabetes in a subject; a method of screening for an agent that treats a metabolic disease; delivery of PBK-1 DNA to a subject to stimulate pancreatic beta cell differentiation and/or regeneration; a method for stimulating cell differentiation and/or regeneration in a pancreatic beta cell; usage of transgenic mice with targeted deletion or overexpression of the PBK-1 gene to test efficacy and specificity of PBK-1 modulator compounds.