Abstract: Methods and compositions relating to Alzheimer's disease are provided, including proteins that are differentially expressed in Alzheimer's disease as compared to the normal state. Further provided are methods, particularly experimental paradigms, for the identification of differential expressed proteins that are potential molecular targets for compounds to treat or prevent Alzheimer's disease. Also provided are methods for the identification and therapeutic use of compounds for the prevention and treatment of Alzheimer's disease.

Abstract: The present invention provides antibodies that preferentially bind to an ApoE(1-272) fragment relative to ApoE(1-299). These antibodies serve to reduce the toxicity of this fragment and find use in treatment and prophylaxis of a variety of neurological diseases.

Abstract: The subject invention pertains to a non-human animal model of human cancer, methods of producing a non-human animal model of human cancer, methods of using a non-human animal model to propagate human cancer cells, methods of using a non-human animal model to study cancer, methods of using a non-human animal model to screen potential treatments for a subject's cancer, methods of using a non-human animal model for treating cancer in a subject (providing personalized therapy), methods of using a non-human animal model for identifying a biomarker of cancer treatment; and methods of using a non-human animal model for selecting cancer patients for a clinical trial.

Abstract: The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

Abstract: This invention relates to a genetically modified or chimeric rat cell whose genome comprises chromosomal alleles of an obesity-diabetes gene (especially, the Mc4r gene or Lep gene), wherein at least one of the two alleles contains a mutation, or the progeny of this cell. The obesity or diabetes gene may affect any of the pathways of obesity and diabetes. The obesity or diabetes gene may predispose the rat to a phenotype of obese and diabetic, lean and diabetic, obese and non-diabetic, non-obese and diabetic or any of the combinations thereof. In another aspect, the invention relates to a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to obesity or diabetes.

Abstract: The present disclosure relates to an ASD genetically engineered model carrying a deletion of Shank2 gene and having reduced NMDA receptor function. According to the present disclosure, genetically engineered mice that show the clinical features of ASD due to the deletion of the Shank2 gene can be obtained, and the genetically engineered mice can be effectively used to screen candidate therapeutic agents.

Abstract: The present invention provides compositions and methods for studying neuropathy. The compositions and methods provided herein are particularly useful for screening agents of therapeutic and/or diagnostic potential.

Abstract: The present invention provides method for monitoring physiological status of an organ in a subject by monitoring morphological changes over time in transplanted tissue on an eye of the subject.

Abstract: The present invention relates to a transgenic pig as a model for studying a cone affecting disease, in particular a cone dystrophy or cone-rod-dystrophy, wherein the pig model expresses a dominant negative guanylate-cyclase-2D (GUCY2D) protein, in particular a GUCY2D protein comprising at least one mutation responsible for the appearance of a CORD6 cone dystrophy in a human being. The invention further relates to methods by which the transgenic pig is produced, to uses of said transgenic pig or of one of its elements to identify new biomarkers of a cone affecting disease and/or new compounds for preventing or treating such a disease. Novel methods for preventing or treating a cone affecting disease or for evaluating conditions needed to alleviate such a disease are further herein described.

Abstract: The invention relates to the generation of non-human transgenic animals comprising a reporter construct for producing a detectable amount of a reporter molecule operably linked to a transcriptional regulatory nucleic acid molecule from the human CYP3A4 gene located between the initiation of transcription site of the gene and a position located 13,000 nucleotides upstream from the site. The invention also relates to the use of these animals for determining the effect of a compound, particularly, but not exclusively, a xenobiotic or steroid, on the regulation of expression of the CYP3A4 gene in a human.

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. One aspect of the invention relates to the use of a human DNA sequence comprising at least part of introns 6 and/or 7 of the human PXR gene.

Abstract: The present invention provides, inter alia, transgenic non-human animals, such as transgenic mice. The animals contain in their genome a polynucleotide encoding a von Willebrand factor (VWF) polypeptide, which polypeptide forms a thrombus when in the presence of human platelets. Nucleic acid sequences and vectors for generating the transgenic non-human animals, and methods for using the transgenic non-human animals are provided as well. Chimeric VWF proteins are also provided.

Abstract: An animal model for Parkinson's disease has a disrupted Mfn2 gene in dopaminergic neurons.

Abstract: The present invention relates to methods for identifying compounds that modulate untranslated region-dependent expression of a target gene. The invention particularly relates to using untranslated regions of a target gene or fragments thereof linked to a reporter gene to identify compounds that modulate untranslated region-dependent expression of a target gene. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads.

Abstract: Methods of identifying new treatments for schizophrenia, and the use of the same.

Abstract: The present embodiments relate to methods of identifying and creating human or humanized antibodies that possess a reduced risk of inducing a Human Anti-Human Antibody (HAHA) response when they are applied to a human host. Other methods are directed to predicting the likelihood of a HAHA response occurring. Methods for screening for anti-HAHA compounds are also included. Methods for determining if various conditions for administering an antibody to a subject enhance or suppress a HAHA response are also included.

Abstract: The invention relates to a novel polypeptide vitamin K epoxide recycling polypeptide (VKORC1) as a target for coumarin and its derivatives. The invention further provides methods for identifying coumarin derivatives, and also claims VKORC1 polypeptides and VKORC1 nucleic acids containing a sequence abnormality associated with a VKORC1 associated deficiency such as warfarin resistance, wherein the VKORC1 polypeptides and VKORC1 nucleic acids can be used for diagnosing these deficiencies. Moreover, the invention relates to methods for identifying coumarin derivatives usable in pest control of rodents.

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: Provided herein are compositions and methods for disrupting at least one reward-related behavior in an individual through the use of light-responsive opsin proteins used to control the polarization state of the cholinergic interneurons of the nucleus accumbens or the striatum.

Abstract: The present invention relates to a non-human animal deficient in the N-terminal domain of the IL-33 gene. Also provided herein is the use of said non-human animal as an in vivo model of inflammatory diseases, especially with regard to screening methods for anti-inflammatory compounds, and methods for evaluating and optimising the pharmacological properties of a given anti-inflammatory compound.

Abstract: Disclosed is an evaluation method which can rapidly discriminate a Dao?/? homozygote from a large number of animals produced in a mating experiment between a DAO enzyme deficient mouse and other disease model mice, to rapidly perform a quantitative measurement of the D-amino acids contained in a large number of samples. The invention provides a method for evaluating the effect of a test condition on a mouse tissue, or cultured tissue cells derived from the tissue. The method comprises the steps of: providing a Dao1?/? mouse or the like; exposing the tissue from the Dao1?/? mouse or the like, to the test condition; and analyzing the effect of exposing the tissue from the Dao1?/? mouse or the like, to the test condition.

Abstract: Methods and compositions are provided for modulating, e.g., reducing, coding sequence expression in mammals. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is administered to a non-embryonic mammal, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

Abstract: Disclosed are methods and compositions for treating subjects with Cornelia de Lange Syndrome (CdLS). Specifically disclosed are methods for using Indomethacin or Acemetacin to treat subjects with CdLS. Also disclosed are methods for identifying compounds beneficial for the treatment of CdLS using an assay based on the expression of NIPBL or NIPBL homologous or orthologous genes. Also disclosed is a method of identifying compounds beneficial for the treatment of CdLS based on administering a test compound to Drosophila lava with reduced expression of Nipbl, and determining the normalization of CdLS phenotypes.

Abstract: Provided herein are rodents that express the human endosialin gene. In preferred embodiments, the rodent is a mouse. Preferably, the human endosialin gene is integrated into the native or endogenous endosialin gene locus. More preferably, the host rodent is null for the endogenous endosialin gene product. The human endosialin gene is preferably expressed in a similar development and disease response pattern as that of the native endosialin gene product in parental or wild type rodents. This feature makes these rodents useful for studying the effects of test agents to positively or negatively affect endosialin biology for therapeutic use. Use of human endosialin expressing rodents lacking native endosialin gene product (HUE rodents) is proposed as a strategy for developing agents that can positively or negatively affect the endosialin pathway and also serve as a screening tool to identify those agents that may be useful as human therapies.

Abstract: The present invention provides a nucleic acid construct for expressing an oxidative stress indicator comprising: a nucleic acid sequence encoding an Nrf2 protein-derived partial protein that comprises at least an Neh2 domain sequence and substantially lacks or is functionally deficient in an Neh1 domain sequence or an Neh1-Neh3 domain sequence; a stress-inducible promoter sequence positioned upstream of the nucleic acid sequence encoding an Nrf2 protein-derived partial protein; and a nucleic acid sequence encoding a protein capable of generating a detectable signal, the nucleic acid sequence being positioned downstream of the nucleic acid sequence encoding an Nrf2 protein-derived partial protein. The present invention also provides a method for measuring oxidative stress and a method for screening for an anti-oxidative stress agent, using the nucleic acid construct.

Abstract: The present invention relates to transgenic animals comprising a mutation or deletion to the ANF-RGC protein, particularly to its ARM and/or its ATS-ST region. Such animals may be used to study the effects on pathways associated with ANF-RGC activation, including, but not limited to, hypertension. Such animals may also be used in drug screen assays, to establish toxicity profiles, or other similar methods discussed herein known in the art.

Abstract: A knock-out non-human animal, in particular a mouse, carrying a QPCTL knock-out mutation. Additionally, respective cells and cell lines and methods and compositions for evaluating agents that affect QPCTL, for use in compositions for the treatment of QPCTL-related diseases are disclosed.

Abstract: A zebrafish seizure model, a method for establishing the same, and a method for screening for antiepileptic drug using the same are disclosed. The method for establishing the zebrafish seizure model comprises the following steps: placing a zebrafish in a medium containing an inducing compound represented by the following formula (I) to induce seizure-like symptom in zebrafish: wherein, the definitions of R1, R2, R3 are the same as those defined in the specification.

Abstract: The present 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 cytokine-cytokine mediated autoimmune and inflammatory disease. 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 human autoimmune and inflammatory disease and methods of their use. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a cytokine gene such as the Faslg gene, the Fas gene, etc. In one embodiment, the cytokine gene is the Faslg gene. In another embodiment, the cytokine gene is one of several known cytokine genes, such as Fas, IFN?, TNF-?, IL-2, IL-10, and IL-12.

Abstract: A non-human animal model for muscle cell atrophy is provided. In certain embodiments, the animal comprises a cell comprising a nuclear genome comprising a biologically active atrogen gene in operable linkage with a reporter construct comprising: i. a first coding sequence for an optically detectable protein; and ii. a second coding sequence for a secreted reporter enzyme; wherein expression of the atrogen gene is induced upon initiation of muscle cell atrophy, thereby resulting in production of the secreted reporter enzyme and the first optically detectable protein by the cell. Screening assays that employ the non-human animal are also provided.

Abstract: A transgenic animal other than human in which neuropsychiatric disorder condition is developed by the deletion of an HB-EGF gene is obtained. The present invention relates to a transgenic animal other than human in which an HB-EGF gene is deficient and neuropsychiatric disorder condition is developed, and a production method thereof, and a method for screening a therapeutic agent for neuropsychiatric disorder. As a transgenic animal in accordance with the present invention, a transgenic animal in which an HB-EGF gene is specifically deficient in the spiny neurons (striatum, and hippocampus) can be obtained by crossbreeding a transgenic animal that contains a genotype of Gng7(+/cre), and a transgenic animal that contains a genotype of Hb-egf(flox/flox).

Abstract: Provided is a method of using any mammal except humans, in particular, a mammal as an attention deficit hyperactivity disorder model, wherein genes of G protein-coupled receptor kinase interacting protein 1 (GIT1) as a neuronal synapse protein in the brain are knocked out from the mammal. In addition, disclosed is analysis of GIT1 knock-out mice in aspects of molecular biology, cellular biology, electrical biology and animal behavior and, more particularly, a screening method of novel drug, wherein excessive behavior as an attention deficit hyperactive disorder as well as recovery of theta wave in the frontal lobe are observed by administering a candidate material of the drug, thereby inducing recovery of the attention deficit hyperactivity disorder.

Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Abstract: The present invention relates to a genetically modified pig as a model for studying atherosclerosis. The modified pig model displays one or more phenotypes associated with atherosclerosis. Disclosed is also a modified pig comprising a mutation in the endogenous ApoE gene or part thereof, LDL gene or part thereof, LDL receptor gene, or transcriptional or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of atherosclerosis; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from atherosclerosis are disclosed.

Abstract: A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Abstract: The present invention provides methods and compositions for modulating the activity of phosphodiesterase 1B (PDE1B) in intracellular signaling pathways, including but not limited to, dopamine D1 intracellular signaling pathways. The invention also provides methods and compositions for modulating the activities of intracellular signaling molecules, including, but not limited to, DARPP-32 and GluR1 AMPA receptor, via modulation of PDE1B. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate PDE1B activity. The invention also provides methods of treating or ameliorating the symptoms of a disorder, including but not limited to a PDE1B-related disorder or a dopamine D1 receptor intracellular signaling pathway disorder, by administering a modulator of PDE1B, preferably, but not limited to, an inhibitor of PDE1B or an agent that decreases the production of PDE1B.

Abstract: Methods for treating neurological diseases and for testing Caloric Restriction (CR) mimetics or CR mimetic candidates. In one exemplary method, a CR mimetic candidate is administered to a transgenic animal and the effects of the administering are determined; the transgenic animal includes an added gene from another type of animal or a modified gene which is designed to produce a disease or ailment of another type of animal, and the method seeks to determine whether the CR mimetic candidate improves the disease or ailment. Methods relating to neurological disease and other methods relating to CR mimetic testing are also described.

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 a ?-L-iduronidase knock-out mouse. More particularly, this invention relates to a ?-L-iduronidase knock-out mouse to be designed for developing a treatment or an agent for mucopolysaccharidosis type I (Hurler syndrome or Hurler-Scheie syndrome) as an animal model.

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: Provided are a novel probe for a hair cell for clearly identifying various conditions of a hair cell, and a labelling method for a hair cell using the probe for a hair cell, more particularly, a probe for a hair cell containing, as an active agent, at least one kind selected from staining compounds represented by one of the general formulae (I) and (II), and a labelling method for a hair cell using the probe for a hair cell.

Abstract: Disclosed herein are naphthoquinone analogs, such as plumbagin, pharmaceutical compositions that include naphthoquinone analogs, such as plumbagin, and methods of treating diseases and/or conditions such as cancer with naphthoquinone analogs, such as plumbagin. Also included are combination therapies wherein a naphthoquinone analog, such as plumbagin, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.

Abstract: The present invention is directed to fish whose genome has integrated therein an oncogenic nucleic acid operably linked to a promoter. Methods of making the fish and methods for their use are also provided. The fish may advantageously be utilized in methods of screening for drugs or agents that modulate oncogene-mediated neoplastic or hyperplasic transformation, or that modulate sensitivity to chemotherapy or radiation therapy. Immortal tumor cells lines, methods of making immortal tumor cells lines and methods of their use are also provided.

Abstract: A method is disclosed involving detecting the expression of a fluorescent protein of interest in an animal, wherein the animal is a transgenic animal having in its genome nucleic acid encoding said fluorescent protein operably linked to promoter nucleic acid from a protein that is normally expressed in the nervous system of the animal, the method comprising the step of non-invasively detecting fluorescence from said protein when expressed in said animal.

Abstract: Human PFK genes are identified as modulators of the IGFR pathway, and thus are therapeutic targets for disorders associated with defective IGFR function. Methods for identifying modulators of IGFR, comprising screening for agents that modulate the activity of PFK are provided.

Abstract: It has been discovered that STAT5 phosphorylation and CD150 are effective biomarkers for detecting, diagnosing, and monitoring hematological malignancies, including for example lymphomas. Compositions and methods for identifying therapeutic agents for the treatment of hematologic malignancies using p-STAT5, CD150 or both as biomarkers are described.

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

Abstract: The invention provides transgenic animals having a transgene comprising a genomic human alpha synuclein segment including six exons, five introns and at least one mutation associated with synucleinopathic disease operably linked to a human alpha synuclein promoter. The transgenic animals have characteristics of synucleinopathic disease including elevated levels of alpha synuclein in the brain, formation of intracellular deposits of alpha synuclein that have at least one, and preferably all features of Lewy bodies, formation of alpha-synuclein fragments, or phosphorylated forms of alpha synuclein, loss of neuronal cells, glial cells or oligodentricytes, impairment of motor function and/or impairment of cognitive function.

Abstract: The present disclosure describes an animal model of central neuropathic pain relevant to spinal cord injury, as well as methods of using the model to screen for therapeutic agents and to test existing therapies.

Abstract: A lentiviral vector was used to produce non-human animals that express human sFLT1 specifically in the murine placenta, to provide model animals of diseases such as pregnancy-induced hypertension syndrome that are close to the clinical conditions, methods for producing the model animals, methods of screening for candidate compounds as therapeutic agents for diseases such as pregnancy-induced hypertension syndrome by using the model animals, and therapeutic agents for diseases such as pregnancy-induced hypertension syndrome. As a result, the model animals were found to exhibit symptoms that are very close to the clinical conditions in human, which are presentation of hypertension as well as placental insufficiency, intrauterine growth retardation, glomerulosclerosis, and proteinuria during pregnancy, and improvement of those symptoms postpartum.