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 for anrelate to an animal model for characterizing emesis, and for screening and characterizing emetic and antiemetic agents. In several embodiments, the Least Shrew, Cryptotis parva, provides a specific and rapid behavioral animal model to screen concomitantly both the CNS penetration and the antiemetic potential of antiemetic agents to relieve, for example, chemotherapy-induced emesis.

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: An object of the present invention is to develop a new alternative splicing reporter system and to provide a method for detecting alternative splicing patterns in a multicellular organism more precisely, a method for identifying efficiently substances and gene regions that affect alternative splicing in a multicellular organism, and the like by utilizing the alternative splicing reporter system. Specifically, the present invention relates to a method for detecting alternative splicing in a multicellular organism, and a method for identifying substances and gene regions that affect alternative splicing in a multicellular organism, which use a DNA construct in which at least two different reporter genes are inserted into a specific gene that undergoes alternative splicing, or a combination of DNA constructs (a combination of at least two different DNA constructs) in which DNA construct a reporter gene is inserted into a specific gene that undergoes alternative splicing.

Abstract: Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

Abstract: Disclosed herein are methods of identifying inhibitors of gene silencing or re-silencing, which can include repressing expression of a selectable marker gene in mammalian cells, treating the cells with at least one test compound, growing the cells under selective conditions, and quantifying the relative number of cells that live, wherein a change in the relative number of cells as compared to cells that were not treated with the test compound, identifies the compound as an inhibitor of gene silencing or re-silencing. Also disclosed herein are transgenic mice and isolated cell lines that are useful in the disclosed methods and kits for use in performing the disclosed methods.

Abstract: The present invention relates to a new family of structurally and functionally related nucleic acids and proteins, designed the CATERPILLER family, which is characterized by landmark structural motifs including a nucleotide binding domain and leucine-rich repeat domains.

Abstract: The method of the invention is useful for evaluating pharmaceutical compositions for treatment of neurological diseases encompassing neurological or neurodegenerative diseases associated with cognitive dysfunction and, in particular, dementia; schizophrenia; anxiety; depression; and pain using a rodent behavioral assay, wherein the method is useful in testing compositions useful in the modulation, amelioration, prevention, or treatment of dementia using a non-human animal carrying at least a transgene for human amyloid-beta protein or human tau and transgenes causing the elevated production of the human amyloid-beta protein in the animal as compared to nontrans genie animals of the same genetic background and the behavior is a nesting behavior.

Abstract: The invention relates to an animal model of cardiovascular disease and a method of preparation and use thereof. In particular, it relates to a genetically engineered animal model of aortic aneurysms and methods for screening drugs using the animal model. Provided is a genetically-modified, non-human mammal, wherein the modification results in a disrupted Fibulin-4 gene. Also provided is a genetically-modified animal cell containing a disrupted Fibulin-4 gene. The mammal or animal cell can be used as a model for a cardiovascular condition or disease, preferably aortic aneurysm, more preferably thoracic aortic aneurysm. Furthermore, methods for identify or validating a compound that can be used to treat or to prevent an aberrant cardiovascular condition are provided, as well as method to identify a gene involved in the response to aortic failure.

Abstract: The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter; and (b) a DNA sequence which encodes a receptor for advanced glycation endproducts (RAGE), wherein the promoter and the DNA sequence which encodes the receptor for advanced glycation endproducts (RAGE) are operatively linked to each other and integrated in the genome of the non-human animal, and wherein said non-human animal exhibits a reduced amount of cerebral tissue infarcted following a transient middle cerebral artery occlusion compared to an identical non-human animal lacking said DNA sequence.

Abstract: A method for testing compound for a therapeutic effect utilizing a non-human animal or cell having disruption in the prostatic acid phosphatase gene resulting in a decrease or absence in the activity or the level of prostatic acid phosphatase. The compound may be used for treating disorders related to unbalanced phosphatidylinositol phosphate cascade or signaling pathway. Diagnostic methods and methods for treating the disorders with therapeutic compounds or by gene therapy are also disclosed.

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: The present invention relates, generally, to a transgenic non-human animal model of hemophilia A, wherein the transgenic animal is deficient in endogenous Factor VIII and endogenous von Willebrand Factor, and methods to treat hereditary or acquired hemophilia A or von Willebrand Disease (VWD) by administration of exogenous human VWF.

Abstract: The present invention relates to mutant animals having a modified NMDA Receptor and use of the same for screening compounds useful for treating psychiatric and neurological disorders, such as schizophrenia, autism and Alzheimer's Disease. In particular, the invention provides an animal model that has mutation in phosphorylation of the NR1 subunit of the NMDAR, which causes behavioral deficits associated with psychiatric disorders useful for the evaluation of the therapeutic effects of psychotropic drugs for the treatment of these disorders.

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

Abstract: The present invention relates to a transgenic animal wherein DNA encoding p300 and a promoter exerting its activity in myocardial cells are introduced, and a screening method using the same.

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 PRO196, PRO217, PRO231, PRO236, PRO245, PRO246, PRO258, PRO287, PRO328, PRO344, PRO357, PRO526, PRO724, PRO731, PRO732, PRO1003, PRO1104, PRO1151, PRO1244, PRO1298, PRO1313, PRO1570, PRO1886, PRO1891, PRO4409, PRO5725, PRO5994, PRO6097, PRO7425, PRO10102, PRO10282, PRO61709 or PRO779 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: Methods of treatment, diagnosis and screening related to GAPR-1 are disclosed.

Abstract: The invention is an animal model which exhibits neuropathological and behavioral features associated with human schizophrenia. The invention also encompasses an in vivo method of preparing an animal model of human schizophrenia. Such a model is useful for screening and identifying therapeutic agents for treating human schizophrenia.

Abstract: Provided are non-human mammals comprising a transgenic nucleic acid sequence capable of causing an alteration of expression of Bri2 or Bri3 in the mammal. Also provided are non-human mammals comprising a Bri2 or Bri3 gene under the control of the native Bri2 or Bri3 promoter. Additionally provided are non-human mammals genetically engineered to lack expression of a Bri2 or Bri3 gene. Further, non-human mammals comprising a transgene encoding a Bri2 or Bri3 protein under the control of the ?CaMKII promoter are provided. Non-human mammals comprising a transgene encoding a furin protein are additionally provided. Embryonic stem cells of any of the above-described non-human mammals are further provided. Methods of screening a compound for treatment of a disease characterized by cerebral amyloidosis are additionally provided. Also provided are methods of making transgenic non-human mammals.

Abstract: Keratin 8 and 18 (K8/K18) mutations are shown to be associated with a predisposition to liver or biliary tract disease, particularly noncryptogenic hepatobiliary disease. Unique K8/K18 mutations are shown in patients with diseases including but without limitation to viral hepatitis, biliary atresia, alcoholic cirrhosis and other acute or chronic toxic liver injury, cryptogenic cirrhosis, acute fulminant hepatitis, autoimmune liver disease, cystic fibrosis, primary biliary cirrhosis, primary sclerosing cholangitis, diseases that are linked with cryptogenic cirrhosis, such as nonalcoholic steatohepatitis, and the like. Livers with keratin mutations had increased incidence of cytoplasmic filamentous deposits. Therefore, K8/K18 are susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease. Mutant alleles are associated with disease susceptibility, and their detection is used in the diagnosis of a predisposition to these conditions.

Abstract: A rat with a disrupted Apc (adenomatous polyposis coli) gene is provided. The mutation can include an A to T transversion changing a lysine to a stop codon at codon 1137. Methods of generating the knockout rat are provided. Also provided is the offspring or progeny of that rat. In addition, methods of using these rats are provided, including methods for screening a carcinogen or a promoter of carcinogenesis, and methods for screening preventive and inhibitory agents of carcinogenesis.

Abstract: The invention provides non-human transgenic animals as models of neurodegenerative brain pathology, including, but not limited to, Alzheimer's disease (AD), and cancer. The non-human transgenic animals of the present invention include an exogenous DNA that reduces or eliminates the expression and/or function of a molecular chaperone, including, but not limited to heat shock protein 110 (Hsp1 10) or heat shock protein 70 (Hsp70). These non-human transgenic animals may be used in methods of screening and identifying compounds useful for the prevention and/or treatment of neurodegenerative brain pathology and/or cancer.

Abstract: Provided herein is a recombinant non-human mammal having an immune system including human immune cells and having a liver including human liver cells, and methods for producing the same. Also provided are methods of screening a compound for activity in treating hepatitis, comprising: administering a test compound to a recombinant non-human mammal as described herein; and then detecting the presence or absence of said activity in said mammal (e.g., by biochemical assay), said presence of said activity in said mammal indicating that said compound has activity in treating hepatitis. Methods of making fusion cells useful for the production of human monoclonal antibodies are also provided.

Abstract: The present invention relates to a transgenic animal suitable for modelling Alzheimer's Disease. The present invention also relates to cells and gametes of the transgenic animal of the invention, along with nucleic acids and vectors suitable for generating the transgenic animal. Methods of generating the transgenic animal are also described, along with screening methods utilizing the transgenic animal.

Abstract: Novel chimeric proteins are disclosed. The proteins comprise at least two portions. The first portion binds to a first cell and decreases the cell's ability to send a trans signal to a second cell; the second portion sends its own trans signal to the second cell. Methods for making and using these proteins in the treatment of cancer, viral infections, autoimmune and alloimmune diseases are also disclosed, as are pharmaceutical formulations comprising the novel chimeric proteins and genes. Either the proteins themselves or a genetic sequence encoding the protein can be administered. Other methods are also disclosed in which two molecular components result in decrement of a first trans signal from a first cell and the conferring of a second trans signal to a second cell.

Abstract: Disclosed herein are transgenic mouse tumor models. A portion of the cells of the disclosed transgenic mice undergo directed somatic recombination and the mouse is therefore a mosaic for homozygous knockout of p53, NF1, or both p53 and NF1 genes. The homozygous null cells resulting from the somatic recombination also express a detectable fluorescent protein, and the resulting sibling cells, which are wild type for p53, NF1, or both p53 and NF1, express a different detectable fluorescent protein. Also disclosed herein are methods of identifying compounds for treating or preventing a tumor, using the disclosed transgenic mice.

Abstract: The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to alterations in drug and chemical metabolism by modification of its structure or mechanism. 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 drug metabolism gene such as the Cyp7b1 gene, the Cyp3a4 gene, etc. In another embodiment, the rat cell is a somatic cell. The inactivation of at least one drug metabolism allele results in an animal with a higher susceptibility to altered drug and chemical metabolism. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for altered drug and chemical metabolism or toxicology and as a test animal for autoimmune and other studies. The invention additionally pertains to the use of such rats or rat cells, and their progeny in research and medicine.

Abstract: This invention provides methods of diagnosis, drug screening, and treatment based on the discovery that cIAP1 and Yap are co-amplified oncogenes that cooperate to contribute to oncogenesis and tumor maintenance.

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 features a transgenic mouse model of cancer, exemplified by basal cell carcinoma, which finds use in identification of anti-cancer drugs. The transgenic mouse is characterized by a heterozygous defect in a Patch gene (Ptch+/?) and an inducible suppression of functional p53.

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

Abstract: The invention relates to a method for screening a pharmaceutical for treating or preventing a neurodevelopmental disorder or a psychiatric disorder accompanied by an abnormality of oxytocin system by using an increase in expression or enzymatic activity of CD38 as an index, and a diagnosis of a predisposition to a neurodevelopmental disorder or a psychiatric disorder accompanied by an abnormality of oxytocin system by using a mutation present in a CD38 gene region as an index.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences associated with schizophrenia. 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 associated with schizophrenia 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 associated with schizophrenia.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with addiction disorders. 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 encoding addiction-related proteins and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for addiction and withdrawal side effects and other effects.

Abstract: This invention relates to a mammalian artificial chromosome vector, which retains a human chromosome 7 fragment comprising human cytochrome P450 genes and is transmittable to progeny, wherein the human chromosome 7 fragment retains a region of approximately 1 Mb±500 Kb in size comprising at least a human CYP3A gene cluster, which region is located between chromosome markers AC004922 and AC073842, and to a non-human mammalian animal retaining the vector.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated ALS. 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 screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with Parkinson's disease. 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 PD development and screen agents for assessing their effect on progression or symptoms of PD.

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

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: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with cognitive disorders. 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 screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression. 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 tumor suppression and the nucleic acids encoding the 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 tumor suppression.

Abstract: The use of the human or animal MCM9 gene, or parts of the gene, or transcripts thereof, or antisense nucleic acids able to hybridize with part of the gene or transcripts, or silencing RNA derived from parts of the transcripts and able to repress the MCM9 gene, or proteins or peptidic fragments translated from the transcripts, or antibodies directed against the proteins or peptidic fragments, for the preparation of a pharmaceutical composition for the treatment of a human or animal pathology linked to a dysfunction of the expression of the MCM9 gene, or of human or animal cancers.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with ASD. 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 ASD development and screen agents for assessing their effect on progression or symptoms of an ASD.

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: The present invention relates to a fusion protein comprising a Caspase domain or a functionally active variant thereof and a ligand binding domain of a nuclear hormone receptor, a nucleic acid coding for the fusion protein, a vector or cell comprising the nucleic acid, a method of producing the fusion protein, a non-human transgenic animal containing the nucleic acid, the use of the fusion protein for ligand-mediated induction of apoptosis of a cell, or for studying the function of a cell, tissue and/or organ or the use of a transgenic organism for studying the function of a cell at various developmental stages or as a disease model, a method for inducing apoptosis of a cell expressing a fusion protein or for identifying a ligand, or a medicament comprising a fusion protein, the nucleic acid, the vector or the cell, particularly for the treatment of cancer or for or after transplantation, particularly as safety mechanism.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with a secretase disorder. 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 screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with neurodevelopmental disorders. 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 screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal involved in cardiovascular disease. 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 sequences involved in cardiovascular disease and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.