Method Of Using A Transgenic Nonhuman Animal In An In Vivo Test Method (e.g., Drug Efficacy Tests, Etc.) Patents (Class 800/3)
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Publication number: 20130191931Abstract: Described herein is the generation of Fah+/? heterozygote pigs by homologous recombination and somatic cell nuclear transfer, and a method for producing Fah?/? homozygote pigs. The Fah-deficient pigs of the disclosure can be used for a variety of research and therapeutic purposes, such as for the expansion of human hepatocytes, and as large animal models of hereditary tyrosinemia type 1, cirrhosis and hepatocellular carcinoma.Type: ApplicationFiled: March 23, 2011Publication date: July 25, 2013Applicants: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH, OREGON HEALTH & SCIENCE UNIVERSITYInventors: Markus Grompe, Scott Nyberg, Joseph Lillegard, Raymond Hickey
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Patent number: 8492610Abstract: The present invention relates to the field of transgenic animal models and more particularly the animal models of Alzheimer's disease. The invention relates to a transgenic animal expressing a multimutated form of presenilin 1 and allowing an apoptotic phenomenon to be detected in a renewable peripheral tissue.Type: GrantFiled: September 22, 2000Date of Patent: July 23, 2013Assignee: Aventis Pharma S.A.Inventors: Anne Eckert, Walter Muller, Christian Czech, Laurent Pradier, Gunter Tremp
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Publication number: 20130184321Abstract: The present invention relates to an Attention deficit and hyperactivity disorder (ADHD) mouse model and a screening method for a composition for the prevention and treatment of attention deficit disease. The mouse model constructed by inserting cobalt wire in the right side of the frontal lobe is very useful as the ADHD mouse model, and the said ADHD mouse model can be effectively used for the screening of an agent for the treatment of attention deficit disease since the mouse demonstrated brain wave with low frequency, hyperactivity, and cognitive impairment, which are characteristic symptoms of attention deficit disease, when ethosuximide, one of T-type calcium channel blockers, was administered. Therefore, the composition comprising a T-type calcium channel blocker was also confirmed to be effectively used for the prevention and treatment of attention deficit disease.Type: ApplicationFiled: January 21, 2011Publication date: July 18, 2013Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYInventors: Daesoo Kim, Jeongjin Kim
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Publication number: 20130179998Abstract: The present invention describes a novel transgenic mouse model for the common sporadic form of Alzheimer's disease. More particularly, the invention relates to a nucleotide sequence encoding A? 4-42 in functional linkage with at least a promoter, signal peptide sequence and a polyadenylation signal sequence, a cell and a transgenic non-human animal comprising said nucleotide sequence, and their respective use in screening methods.Type: ApplicationFiled: June 8, 2010Publication date: July 11, 2013Inventors: Thomas Bayer, Oliver Wirths
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Publication number: 20130179997Abstract: The present invention provides transgenic non-human animals and non-human mammalian somatic and germ cells harbouring a human DNA sequence encoding Alzheimer's Disease (AD) derived tau protein, capable of inducing AD pathology in transgenic animals. Alzheimer's tau protein is expressed on specific genetic backgrounds allowing also simulation of different human diseases including hypertension, diabetes, hyper-cholesterolemia, which are associated with neurodegeneration and are considerable risk factors for AD development. Transgenic animals and cells of the invention exhibit neurofibrillary pathology and may serve as in vivo and in vitro assay systems for screening and developing therapeutic and preventive substances and also diagnostic markers and probes for tauopathies and AD.Type: ApplicationFiled: September 14, 2012Publication date: July 11, 2013Inventors: Eva KONTSEKOVÀ, Peter FILIPCIK
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Publication number: 20130174284Abstract: The present invention relates to a recombinant vector and a transgenic mouse for expressing human ferritin in a tissue non-specific manner, and more particularly, to a vector prepared by operably linking a human ferritin gene to a promoter including a cytomegalovirus (CMV) early enhancer element and a ?-actin promoter, and a transgenic mouse expressing human ferritin in a tissue non-specific manner, which is transformed with the vector. Further, the present invention relates to a method for preparing a transgenic mouse, and a method for monitoring cell or tissue therapy using the transgenic mouse.Type: ApplicationFiled: July 7, 2011Publication date: July 4, 2013Applicant: SNU R&DB FOUNDATIONInventors: Woo Kyung Moon, Hoe Suk Kim
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Publication number: 20130174285Abstract: The present invention prepared a non-human animal in which Fgf18 gene was knocked out in a keratin-5 positive cell-specific manner using a Cre-loxP system; it provides a non-human model animal in which FGF18 expression has been inhibited in a hair follicle-specific manner to shorten the telogen phase of hair growth cycle. The non-human model animal is useful in studying hair follicles and skin, particularly hair growth occurring cyclically in hair follicle cells, and is applicable to the development of and screening for novel drugs against hair follicle or skin disorders.Type: ApplicationFiled: September 16, 2011Publication date: July 4, 2013Inventors: Toru Imamura, Miho Ueki, Yuko Oda
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Patent number: 8476484Abstract: The invention relates to transgenic aquatic animals, particularly the clawed frog and the zebra fish and cells derived therefrom, characterized in comprising at least one expression cassette with a regulatory DNA sequence selected from the response elements to nuclear hormone receptors, particularly TRE, connected in a functional manner downstream of a DNA segment coding for a marker protein such as luciferase or GFP. The invention further relates to methods using the transgenic cells and animals according to the invention for the identification of endocrine disrupters in the environment.Type: GrantFiled: May 27, 2003Date of Patent: July 2, 2013Assignees: Centre National de la Recherche Scientifique (CNRS), The Museum National d'Histoire NaturelleInventors: Barbara Demeneix, Nathalie Turque
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Patent number: 8476485Abstract: A non-human animal model for amyotrophic lateral sclerosis (ALS) is disclosed. The animal model comprises a rodent whose spinal cord motor neurons have a loss of TAR-DNA binding protein-43 (TDP-43) function and phenotypes exhibit ALS-like symptoms. A method for identifying a candidate agent for treating, preventing and/or inhibiting ALS associated with a loss-of-function of TDP-43 is also disclosed.Type: GrantFiled: June 22, 2011Date of Patent: July 2, 2013Assignee: Academia SinicaInventors: Che-Kun James Shen, Lien-Szu Wu
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Patent number: 8470594Abstract: Disclosed are embryonic stem cells and motor neurons derived from mice carrying transgenic alleles of the normal or mutant human SOD1 gene. Also disclosed are in vitro systems employing such SOD1 transgenic motor neurons for the study of neural degenerative disease.Type: GrantFiled: April 15, 2009Date of Patent: June 25, 2013Assignee: President and Fellows of Harvard CollegeInventors: Kevin Eggan, Francesco Paolo DiGiorgio
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Publication number: 20130160151Abstract: The present invention relates to the use of a transgenic non-human animal, such as a mouse, expressing a reporter gene detectable by a chromogenic, luminescent or fluorescent signal which identifies the cells that express Pw1, or of Pw1-expressing cells or tissues isolated therefrom, as a model for screening a candidate substance for its ability to stimulate adult stem cells, or for monitoring cell aging.Type: ApplicationFiled: July 6, 2011Publication date: June 20, 2013Applicant: Universite Pierre et Marie Curie (PARIS 6)Inventors: David Sassoon, Vanessa Besson, Giovanna Marazzi
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Publication number: 20130160150Abstract: The invention provides methods for reducing diabetes susceptibility in a subject and methods for increasing the expression of LL or CLORF32 in a subject. The invention further provides a method for identifying an agent which modulates expression of an Ll RNA or Clorf32 RNA comprising contacting a cell with an agent; determining expression of the Ll RNA or Clorf32 RNA in the presence and the absence of the agent; and comparing expression of the Ll RNA or Clorf32 RNA in the presence and the absence of the agent, wherein a change in the expression of the Ll RNA or Clorf32 RNA in the presence of the agent is indicative of an agent which modulates the level of expression of the RNA.Type: ApplicationFiled: December 12, 2008Publication date: June 20, 2013Applicant: The Trustees of Columbia University in the City of New YorkInventors: Rudolph L. Leibel, Wendy K. Chung, Charles LeDuc, Stuart G. Fischer, Chouinard Roland
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Patent number: 8466339Abstract: Disruption of mitogen inducible gene 6 (Mig-6) in mice by homologous recombination (KO mice) led to early onset osteoarthritis (OA) as revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage and the development of bony outgrowths or osteophytes within the joint space. Because of the striking similarity to human OA, Mig-6 KO mice are a useful animal model for studying the mechanism of this disease and for testing new drugs or therapies for treating OA. These KO mice also developed epithelial hyperplasia, adenoma, and adenocarcinoma in organs such as lung, gallbladder, and bile duct. Mig-6 is therefore a tumor suppressor gene and is a candidate gene for the frequent Ip36 genetic alterations found in lung cancer. It can be used as a tumor biomarker as well as a target for cancer therapy.Type: GrantFiled: June 15, 2006Date of Patent: June 18, 2013Assignee: Van Andel Research InstituteInventors: Yu-Wen Zhang, George F. Vande Woude
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Patent number: 8466340Abstract: The present invention provides mouse models for Pompe disease and methods of using the same to test agents that may be effective in the treatment of Pompe disease.Type: GrantFiled: February 16, 2010Date of Patent: June 18, 2013Assignee: Amicus Therapeutics, Inc.Inventors: Richie Khanna, Matthew J. Toth
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Patent number: 8466338Abstract: 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.Type: GrantFiled: August 19, 2011Date of Patent: June 18, 2013Assignees: Assistance Publique-Hopitaux de Paris, Institut National de la Sante et de la Recherche Medicale (Inserm), Institut Gustave-Roussy, Universite de Versailles-St Quentin en Yvelines, Universite Paris-SudInventors: William Vainchenker, Valérie Ugo, James Chloé, Jean-Pierre Le Couedic, Nicole Casadevall
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Publication number: 20130152222Abstract: The present invention relates to a transgenic fish having at least one genomically integrated expression cassette containing a 5?-regulatory nucleotide sequence responsive to hormones, particularly estrogenic hormones, connected in a functional manner upstream of a nucleotide sequence encoding a reporter protein. The present invention further relates to methods of using the transgenic fish for various purposes, including, for example: (1) identifying estrogenic endocrine disruptors; (2) monitoring estrogen-like activity of test samples; (3) identifying anti-estrogenic endocrine disruptors; and (4) investigating the effects of endocrine disruptors on liver regeneration. Expression cassettes, host cells, and transgenic cells of aquatic animals are also disclosed.Type: ApplicationFiled: February 18, 2013Publication date: June 13, 2013Applicant: CITY UNIVERSITY OF HONG KONGInventor: CITY UNIVERSITY OF HONG KONG
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Publication number: 20130150465Abstract: The present invention relates to a genetically modified pig as a model for studying breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex. The modified pig model displays one or more phenotypes associated with any of said disorders. Disclosed is also a modified pig comprising a modified endogeneous BRCA1 and/or BRCA2 gene, and/or a modified ornithine transcarbamylase gene, and/or a modified Keratin 14 gene and/or a 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 breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex are disclosed.Type: ApplicationFiled: August 22, 2012Publication date: June 13, 2013Applicant: Aarhus UniversitetInventors: Peter Michael Kragh, Lars Axel Bolund, Charlotte Brandt Sørensen, Thomas Juhl Corydon, Niels Gregersen, Peter Bross
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Publication number: 20130139273Abstract: A mouse model and uses there of for detecting, treating, characterizing, and diagnosing various diseases are described.Type: ApplicationFiled: June 20, 2011Publication date: May 30, 2013Applicant: THE OHIO STATE UNIVERSITYInventors: Carlo M. Croce, Yuri Pekarsky
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Publication number: 20130133089Abstract: Leptin muteins, in particular leptin antagonists, with increased binding affinity to leptin receptor are provided. These compounds as well as pharmaceutical composition comprising them are useful for the treatment of any disorder in which a non-desirable or deleterious activity of endogenous leptin or an altered innate immune response is implicated.Type: ApplicationFiled: April 17, 2011Publication date: May 23, 2013Applicants: THE MEDICAL RESEARCH, INFRASTRUCTURE, AND HEALTH SERVICES FUND OF THE TEL-AVIV, YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEMInventors: Arieh Gertler, Eran Elinav, Zamir Halpern
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Patent number: 8445745Abstract: 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.Type: GrantFiled: May 30, 2012Date of Patent: May 21, 2013Assignee: KMT Hepatech, Inc.Inventors: Norman M. Kneteman, D. Lorne Tyrrell, David Frederick Mercer
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Patent number: 8440412Abstract: The present invention provides a complex of an antigen and IgE binding to the antigen, a composition including an antigen and IgE binding to the antigen, and a method of using the complex or the composition to screen candidate therapeutics for TH-2 type diseases, for example in animal models.Type: GrantFiled: October 26, 2009Date of Patent: May 14, 2013Assignee: Hyogo College of MedicineInventors: Kenji Nakanishi, Tomohiro Yoshimoto
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Publication number: 20130117868Abstract: A Myelin Basic Protein-luciferase bioimaging noninvasive model to visualize and quantify demyelination and remyelination events in the CNS at transcriptional level in vivo is provided. Luciferase-expressing transgenic animals were generated with myelin basic protein (MBP) promoter coupled to firefly luciferase reporter. The MBP-luci bioimaging model provides a means to monitor myelination status and the efficacy of a remyelination modulating test compound. An advantage of bioimaging is that a subject in a longitudinal study can serve as its own control. The same subject can be tracked over a demyelination and remyelination process continuously over a period of at least 10 weeks. This model enables normalization of individual animal imaging response and provides quality data with considerably reduced variance. In addition, because cohorts of animals need not be sacrificed at different time points, reduction in the number necessary for a compound efficacy study is possible.Type: ApplicationFiled: December 3, 2010Publication date: May 9, 2013Applicant: SANOFIInventors: James Cao, Karen Chandross, Kyriakos D. Economides, Harry Gregory Polites, Daniel Weinstock, Xiaoyou Ying
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Patent number: 8435488Abstract: 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.Type: GrantFiled: February 25, 2010Date of Patent: May 7, 2013Assignee: Genentech, Inc.Inventors: Herman Gill, Jan Marik, Jeff Tinianow, Simon Williams
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Patent number: 8436224Abstract: 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.Type: GrantFiled: June 6, 2011Date of Patent: May 7, 2013Assignee: BioMarker Pharmaceuticals, Inc.Inventor: Xi Zhao-Wilson
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Publication number: 20130111611Abstract: A method to measure the metabolic rate or rate of glucose consumption of cells or tissues with high spatiotemporal resolution using a glucose nanosensor is disclosed. The method generally includes providing single cells or cell populations, cells in suspension or adherent, in a cell culture, a tissue culture, a mixed cell culture, a tissue explant, or in animal tissues in vivo for the measurement of glucose metabolic rate; expressing a glucose sensor in individual cells; calibrating the sensor in controlled conditions; disrupting the steady-state of glucose entering the cell; recording the output from the sensor and calculating the corresponding glucose concentration at different times; and determining the glucose metabolic rate. The method can be applied for the screening of molecules with pharmacological potential, determination of glucose rate of cancerous cells, tissue physiology and biochemistry research.Type: ApplicationFiled: June 30, 2010Publication date: May 2, 2013Applicants: CARNEGIE, INSTITUTION OF WASHINGTON, CENTRO DE ESTUDIOS CIENTIFICOS DE VALDIVIAInventors: Luis Felipe Barros Almedo, Carla Ximena Bittner Hofmann
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Publication number: 20130109738Abstract: Methods and compositions are provided for the diagnosis and treatment of heart diseases relating to cardiac hypertrophy, and for the regulation of proliferation and differentiation of cardiomyocyte progenitors in vitro. The detection of expression of components of the BAF complex, including, without limitation, detection of expression of Brg1, provides useful methods for early detection, diagnosis, staging, and monitoring of conditions leading to hypertrophy and enlargement of the heart. Manipulation of Brg1 activity provides for therapeutic intervention in the development of cardiac hypertrophy, where methods of decreasing Brg1 activity, e.g. through inhibition of binding, decreasing expression, and the like, reduces cardiac hypertrophy.Type: ApplicationFiled: February 23, 2011Publication date: May 2, 2013Applicant: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Ching-Pin Chang, Calvin Hang, Pei Han, Jin Yang, Ksiu-Ling Cheng
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Patent number: 8431768Abstract: 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 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. promoter and/or enhancer regions) which delimit expression of operably linked gene product(s) to discrete cellular populations; (ii) a gene product that promotes cellular ablation composed of a pro-drug conversion system capable of converting nontoxic pro-drugs into cytotoxic drugs, which is expressed alone or in connection with; (iii) a reporter gene product that allows selective detection of cells expressing the reporter—both prior to (initial cells) and following cellular ablation (regenerated cells).Type: GrantFiled: November 2, 2011Date of Patent: April 30, 2013Assignee: Washington UniversityInventors: Jeffrey S. Mumm, Eric H. Schroeter
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Patent number: 8431767Abstract: Transgenic immunodeficient non-human animals according to embodiments of the present invention are described which include in their genome a nucleic acid encoding xenogeneic Stem Cell Factor operably linked to a promoter. Administration of xenogeneic hematopoetic stem cells to the inventive transgenic animals results in engraftment of the xenogeneic hematopoetic stem cells and xenogeneic leukocytes are produced in the animals, without conditioning such as without conditioning by irradiation and without conditioning by a radiomimetic agent.Type: GrantFiled: November 9, 2010Date of Patent: April 30, 2013Assignees: The Jackson Laboratory, University of Massachusetts Medical SchoolInventors: Leonard D. Shultz, Dale L. Greiner
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Publication number: 20130096067Abstract: The present invention provides a transgenic Drosophila tumor stem cell model and uses thereof. Also provided is a method to selectively inhibit cancer stem cells in a mammal having refractory intestinal cancer or a relapse of intestinal cancer.Type: ApplicationFiled: September 14, 2012Publication date: April 18, 2013Inventors: Norbert Perrimon, Michele Markstein
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Patent number: 8420884Abstract: Methods for screening compounds to treat an oncological disorder regulated through a tumor-inducing pathway are provided. The compounds are administered to non-human animal subjects having a disease model, so that the subjects display pathology symptoms that correspond to the oncological disorder in humans. The subjects carry a regulatable transgene expression, of which is associated with tumor formation, and further carry regulatable genes for suppression of tumor formation. The disease-pathology symptoms are induced using a site-specific recombination system to induce expression of the transgene associated with tumor formation and negatively regulate or eliminate the genes for suppression of the tumor formation. The methods further involve analyzing tumor formation in subjects administered the compound and comparing appearance and amount of tumors in the subjects administered the compound with control subjects not administered the compound.Type: GrantFiled: October 16, 2009Date of Patent: April 16, 2013Assignee: Tufts Medical Center Inc.Inventor: Alain Charest
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Patent number: 8420886Abstract: 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.Type: GrantFiled: July 22, 2005Date of Patent: April 16, 2013Assignee: Erasmus University Medical Center RotterdamInventors: Jeroen Essers, Georgios Aris Garinis, Roland Kanaar
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Patent number: 8420885Abstract: A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumor cells in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.Type: GrantFiled: September 23, 2011Date of Patent: April 16, 2013Assignees: The Regents of the University of Michigan, Oncomed Pharmaceuticals, Inc.Inventors: Michael F. Clarke, Scott J. Dylla, Sanjeev Satyal
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Publication number: 20130091591Abstract: Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis. This distinction can be used to advantage in methods to alter angiogenesis, methods to assess the effect of drugs on artery cells and vein cells, and methods to identify and isolate artery cells and vein cells, for example.Type: ApplicationFiled: August 29, 2012Publication date: April 11, 2013Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Hai U. Wang, Zhoufeng Chen, David J. Anderson
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Patent number: 8415106Abstract: 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.Type: GrantFiled: December 10, 2010Date of Patent: April 9, 2013Assignee: Myelin Repair Foundation, Inc.Inventors: Brian Popko, Wensheng Lin
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Publication number: 20130086701Abstract: A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease and gastric ulcers.Type: ApplicationFiled: August 30, 2012Publication date: April 4, 2013Applicant: THE UNIVERSITY OF CHICAGOInventors: Terence Martin, F. Gary Toback, Margaret Walsh-Reitz
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Publication number: 20130067603Abstract: Nucleic acid and protein sequences relating to a cation channel which is sperm-specific (CatSper4) are disclosed. The CatSper4 protein is shown to be specifically expressed in sperm. Nucleic acids, vectors, transformed cells, transgenic animals, polypeptides, and antibodies relating to the CatSper4 gene and protein are disclosed. Also provided are methods of in vitro fertilization and contraception, methods of identifying modulators of CatSper4 activity, methods of genotyping subjects with respect to CatSper4, and methods of diagnosing and treating CatSper4-mediated disorders, including infertility. Related business methods are also disclosed.Type: ApplicationFiled: February 10, 2012Publication date: March 14, 2013Inventors: Magdalene M. Moran, Jayhong A. Chong, Ian Scott Ramsey, David E. Clapham
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Publication number: 20130067605Abstract: A nucleic acid construct comprising a genetic engineered heterogeneous nuclear ribonucleoprotein (hnRNP) A1 gene is provided. A transgenic mouse in which the expression of hnRNP A1 gene has been disrupted is also provided. The mouse is useful for studying the role of hnRNP A1 gene in normal and disease states of a neurodegenerative disease or a cancer for developing therapies to treat any of these diseases. Therefore, a method of screening a compound for potential use in prevention and/or treatment of neurodegenerative disease or cancer is further provided.Type: ApplicationFiled: August 31, 2012Publication date: March 14, 2013Applicant: KAOHSIUNG MEDICAL UNIVERSITYInventors: Yung-Fu Chang, Ting-Yuan Liu, Yuh-Jyh Jong, Jan-Gowth Chang
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Publication number: 20130067604Abstract: The present application relates to use of a Midkine family protein for growing hair on a mammal, or in the manufacture of a medicament for growing hair on a mammal, especially for treatment or prevention of different forms of alopecia.Type: ApplicationFiled: February 23, 2011Publication date: March 14, 2013Inventors: Sadatoshi Sakuma, Maria Halasz, Darren Jones
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Patent number: 8395018Abstract: The present invention relates to a transgenic fish having at least one genomically integrated expression cassette containing a 5?-regulatory nucleotide sequence responsive to hormones, particularly estrogenic hormones, connected in a functional manner upstream of a nucleotide sequence encoding a reporter protein. The present invention further relates to methods of using the transgenic fish for various purposes, including, for example: (1) identifying estrogenic endocrine disruptors; (2) monitoring estrogen-like activity of test samples; (3) identifying anti-estrogenic endocrine disruptors; and (4) investigating the effects of endocrine disruptors on liver regeneration. Expression cassettes, host cells, and transgenic cells of aquatic animals are also disclosed.Type: GrantFiled: March 24, 2010Date of Patent: March 12, 2013Assignee: City University of Hong KongInventors: Shuk Han Cheng, Xue Ping Chen
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Publication number: 20130061338Abstract: 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.Type: ApplicationFiled: April 13, 2012Publication date: March 7, 2013Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYInventors: Eunjoon KIM, Changwon KANG, Won MAH, Hyejung WON, Eun-Kyoung HAHM, EUNJIN KIM
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Patent number: 8389792Abstract: 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.Type: GrantFiled: March 24, 2010Date of Patent: March 5, 2013Assignee: Cornell UniversityInventors: Laurie H. Glimcher, Wendy Sarah Garrett
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Patent number: 8389794Abstract: The present invention relates to a modified pig as a model for studying Alzheimer's disease. The modified pig model displays one or more phenotypes associated with Alzheimer's disease. Disclosed is also a modified pig comprising a modified human and/or porcine APP gene, and/or PS1 gene, and/or a transcriptional and/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 Alzheimer's disease; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from Alzheimer's disease are disclosed.Type: GrantFiled: March 6, 2008Date of Patent: March 5, 2013Assignee: Aarhus UniversitetInventors: Arne Lund Jørgensen, Ida Elisabeth Holm, Anders Lade Nielsen, Marianne Gregers Johansen, Jannik Ejnar Jakobsen
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Publication number: 20130055417Abstract: The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. The invention also provides methods to transform normal primary cells so cultured into “cancer stem cells.” The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.Type: ApplicationFiled: July 23, 2012Publication date: February 28, 2013Applicants: The Brigham and Women's Hospital, Whitehead Institute for Biomedical ResearchInventors: Tan A. Ince, Robert A. Weinberg
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Publication number: 20130052203Abstract: A double transgenic non-human animal, in particular a transgenic mouse encoding Qpct proteins, which have been implicated in Qpct-related diseases, and Amyloid Precursor Protein (APP). Also provided are cells and cell lines comprising transgenes encoding for Qpct and APP. Also provided are methods and compositions for evaluating agents that affect Qpct, for use in compositions for the treatment of Qpct-related diseases.Type: ApplicationFiled: August 10, 2012Publication date: February 28, 2013Applicant: PROBIODRUG AGInventors: Sigrid Graubner, Wolfgang Jagla, Stephan Schilling, Holger Cynis, Hans-Ulrich Demuth, Torsten Hoffmann, Michael Wermann, Katrin Schulz, Christoph Baeuscher, Stefanie Kohlmann
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Publication number: 20130036481Abstract: The application reports that perlecan domain V (DV) or the LG3 domain thereof reduces deposition and toxicity of A? peptide, the major component of plaques in Alzheimer's disease. Methods of using DV, LG3 and related molecules in treatment of amyloidogenic diseases, particularly Alzheimer's disease, are provided.Type: ApplicationFiled: January 6, 2011Publication date: February 7, 2013Applicant: THE TEXAS A&M UNIVERSITY SYSTEMInventors: Gregory J. Bix, Sarah Wright, Irene Griswold-Prenner
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Publication number: 20130036482Abstract: Provided is a method of assessing a potential for development of Dravet syndrome with high accuracy, and use thereof. The method according to the present invention of assessing a potential for development of Dravet syndrome includes, with use of a sample taken from a subject, detecting whether or not a mutation is on ?-subunit type 1 of voltage-gated sodium ion channel NaV1.1, and detecting whether or not a mutation is on ?-subunit type 1 of voltage-gated calcium ion channel CaV2.1.Type: ApplicationFiled: January 27, 2011Publication date: February 7, 2013Applicant: NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITYInventors: Iori Ohmori, Mamoru Ouchida
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Patent number: 8367887Abstract: 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.Type: GrantFiled: July 11, 2008Date of Patent: February 5, 2013Assignee: Shinshu UniversityInventors: Takuma Hayashi, Yasuko Takahashi, Tomoko Yanagidaira, Shunichiro Taniguchi, Toshinori Murata
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Patent number: 8367364Abstract: The present invention provides methods of screening an agent for an activity in an isolated organ, e.g., eye, from a teleost, e.g., zebrafish. Methods of isolating eyes from zebrafish are provided. Methods of screening an agent for an ocular activity in the isolated eye are provided. Methods of screening an agent for an ocular activity in a model of ocular disease or disorder are provided. Methods of screening an agent for an ocular activity in the isolated eye and for screening the agent for cell death and/or toxic activity in the eye or other organ or tissue are provided. The invention further provides high throughput methods of screening agents for an activity in isolated eyes of zebrafish in multi-well plates.Type: GrantFiled: February 28, 2011Date of Patent: February 5, 2013Assignee: Phylonix Pharmaceuticals, Inc.Inventors: Patricia McGrath, Wen Lin Seng
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Publication number: 20130031644Abstract: Disclosed are systems for expression of an autonomous lux reporter system in a vertebrate cell, such as mammalian or fish cell. In some examples the lux reporter system is operably connected to a pollutant-inducible DNA response element. Also disclosed are transgenic zebrafish, carrying pollution-inducible response elements, and methods of using such zebrafish to monitor pollutants.Type: ApplicationFiled: May 23, 2012Publication date: January 31, 2013Inventors: Steven A. Ripp, Gary S. Sayler, Daniel M. Close, Michelle Connolly, Theodore B. Henry
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Publication number: 20130024955Abstract: The present invention relates to a method for determining a genotoxicity of a test substance, comprising the steps of: (a) transforming a fish with a nucleotide sequence encoding a non-fluorescent fluorescence protein with a mutation; (b) treating a test substance to the transformed fish; and (c) measuring a fluorescence in the test substance-treated fish, wherein the fluorescence is generated by reversion of the non-fluorescent fluorescence protein to the fluorescence protein due to a back mutation of the nucleotide sequence in the test substance-treated fish. According to the present invention, MutaFish system, Zebrafish (Brachydanio rerio) line, in which the fluorescence protein variant, preferably wild type EGFP variant (EGFPmut) is transformed, provides a much excellent animal system for measuring a genotoxicity of a test substance via production of a fluorescent fry larvae generated through reversion of the fluorescent protein variant caused by treatment of the test substance.Type: ApplicationFiled: March 31, 2011Publication date: January 24, 2013Applicant: Industry Foundation of Chonnam National UniversityInventors: Hyon El Choy, Seok-Yong Choi