Abstract: A model rodent animal with a phenotype in which hair growing after birth is black, with the animal spontaneously developing white hair after aging. By way of example, the model rodent animal may have a genotype in which an activated RET gene is genetically inserted in a heterozygous form and the endothelin receptor B gene is deficient in a heterozygous form.
Abstract: The invention provides, among other things, activatable prothrombin, compositions comprising prothrombin, transgenic organisms for making prothrombin, methods for making the transgenic organisms, methods for making prothrombin-comprising compositions and for further purifying prothrombin from the compositions. Illustrative embodiments of the invention particularly provide transgenic mammals that express an exogenous gene for prothrombin and excrete the prothrombin encoded by the gene into their milk. In a highly particular illustrative embodiment in this regard the invention provides transgenic female pigs that express prothrombin in their milk. In this regard, the invention relates particularly to female pigs having stably incorporated in their genomes a DNA comprising a region that encodes prothrombin operably linked to a mammary gland-specific promoter. Further in this regard the invention relates to the milk containing the prothrombin and to prothrombin-containing compositions derived from the milk.
Abstract: A heterologous chimeric animal can be produced by a method comprising the steps of: (A) injecting a stem cell into a blastocyst cavity in a blastocyst stage of an animal heterologous to that of the stem cell, or mixing the stem cell with a divided fertilized egg of the animal heterologous to that of the stem cell; and (B) growing a cell mass including the stem cell prepared in the step (A) into a chimeric animal between a species of the stem cell and a species of the heterologous animal.
Type:
Application
Filed:
January 29, 2010
Publication date:
November 17, 2011
Applicants:
INTER-UNIVERSITY RESEARCH INSTITUTE CORPORATION, THE UNIVERSITY OF TOKYO
Abstract: A non-human transgenic animal having a polynucleotide encoding an STXBP1 polypeptide, which polynucleotide is operably linked to a promoter, wherein said transgenic animal has greater than wild-type expression of the STXBP1 polypeptide in at least one brain region, as well as related vectors, methods of producing transgenic animals, in vitro and in vivo screening methods for potential therapeutic agents, and methods for treating and diagnosing neuropsychiatric illness are disclosed.
Type:
Application
Filed:
August 18, 2009
Publication date:
November 3, 2011
Inventors:
Maria Jose Guerrero Martinez, Laureano Simon Buela, Marcel Ferrer-Alcon, Antonio Martinez Martinez, Jose Javier Meana, Luis Felipe Callado, Leyre Uriguen
Abstract: A sensor system for detecting the activation of specific nuclear receptors in a tissue of an animal is provided. The nuclear receptor sensor system comprises a sensor component comprising a nuclear receptor or part thereof coupled to a DNA-binding domain, and a reporter component comprising a reporter gene. Transgenic animals, such as a transgenic pig is provided, which comprises the components of the nuclear receptor sensor system in its genome. Also methods of producing the transgenic animal is provided as well as use of the transgenic animal for evaluating the activity of a nuclear receptor in vivo.
Type:
Application
Filed:
September 3, 2009
Publication date:
October 27, 2011
Applicants:
SYDDANSK UNIVERSITET, AARHUS UNIVERSITET
Inventors:
Lars Axel Bolund, Karsten Kristiansen, Jacob Giehm Mikkelsen, Nicklas Heine Staunstrup
Abstract: It is revealed that an organ such as pancreas can be regenerated by utilizing a fact that the deficiency of an organ is complemented by injecting an induced pluripotent stem cell (iPS cell) into a developed blastocyst in a blastocyst complementation method. Thus, the present invention has solved the above-described object. This provides a method for producing a target organ, using an iPS cell, in a living body of a non-human mammal having an abnormality associated with a lack of development of the target organ in a development stage, the target organ produced being derived from a different individual mammal that is an individual different from the non-human mammal.
Abstract: Use of an agent which upregulates an activity or amount of miRNA-9 or miRNA-9* is disclosed for the preparation of a medicament for the treatment of a motor neuron disease (MND).
Type:
Application
Filed:
December 3, 2009
Publication date:
September 29, 2011
Applicant:
Yeda Research And Development co., Ltd
Inventors:
Eran Hornstein, Alon Chen, Sharon Haramati, Elik Chapnik
Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
Abstract: The present invention relates to a porcine alpha-S1-casein gene, a porcine alpha-S1-casein gene promoter, an expression comprising the same promoter, and a method for the production of a target protein using the same expression vector. The promoter of the present invention facilitates the mammary gland-specific expression of the target protein. Accordingly, an animal transformed with the promoter secretes the target protein in milk at high concentration, and thus can be advantageously used for the production of useful proteins.
Type:
Application
Filed:
June 29, 2009
Publication date:
September 29, 2011
Inventors:
Myeong Goo Yeo, Sung-Jo Kang, Jong Deok Ahn
Abstract: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.
Type:
Application
Filed:
April 6, 2011
Publication date:
September 22, 2011
Applicant:
KYOWA HAKKO KIRIN CO., LTD.
Inventors:
JAMES M. ROBL, YOSHIMI KUROIWA, POOTHAPPILLAI KASINATHAN, ISAO ISHIDA, KAZUMA TOMIZUKA
Abstract: The present invention relates to use of the GPR30 gene for diagnosis and treatment of cardiovascular disorders, especially cardiomyopathy. The present invention also relates to a GPR30 deficient animal model, more specifically to a mouse in which the GPR30 gene is disrupted and which exhibits a cardiomyopathy, a tissue and a cell of the mouse and a process of producing the same. The present invention further relates to use of said knockout mouse as a model of cardiovascular diseases, especially cardiomyopathy, and a method of screening a compound useful for the prevention and/or treatment of cardiovascular diseases, especially cardiomyopathy, using the knockout mouse.
Abstract: Compositions and methods are provided for screening and identifying compounds which modulate signaling of toll-like receptor 4 (TLR4) pathway via CD 14 and a ligand. Methods are provided for treatment of various disease states such as inflammation or autoimmune disease in mammalian subjects by modulating toll-like receptor 4 (TLR4) pathway signaling via CD 14 and a ligand. Transgenic non-human animals and methods for developing transgenic non-human animals are provided wherein the transgenic non-human animals comprise a loss-of-function mutation in the CD 14 gene.
Abstract: The present invention provides methods for treating a clinical condition associated with lipoprotein lipase activity in the brain of a subject.
Type:
Application
Filed:
November 9, 2009
Publication date:
September 1, 2011
Applicant:
The Regents of the University of Colorado, a body corporate
Abstract: The present invention provides peptides and analogs and derivatives thereof having antimicrobial activity at least against Streptococcus uberis for the treatment of a range of infectious disease mastitis, otitis externa, clostridial intestinal disease and respiratory disease.
Type:
Application
Filed:
March 13, 2009
Publication date:
August 25, 2011
Inventors:
Benjamin Cocks, German Spangenberg, Jianghui Wang
Abstract: The present invention provides a porcine beta-casein gene, a porcine beta-casein gene promoter, an expression vector comprising the same promoter, and a method for the production of a target protein using the same expression vector. The promoter of the present invention facilitates mammary gland-specific expression of the target protein and therefore can be useful for high-concentration production of beneficial proteins in milk.
Type:
Application
Filed:
December 31, 2008
Publication date:
August 25, 2011
Inventors:
Jin Hoi Kim, Myeong Goo Yeo, Sung-Jo Kang, Jong Deok Ahn
Abstract: The genome of the non-human mutant mammal, deficient in an endogenous Sigma receptor, contains a mutation that comprises a disruption in an endogenous Sigma receptor gene, wherein said gene disruption gives rise to a mutant lacking detectable levels of endogenous Sigma receptor. The mutant may be used as a control animal for in vivo tests, as well as a source of cells that can be used in in vitro tests. Mutants deficient in the Sigma-1 receptor can be used as models for in vivo study of disorders of the central nervous system, memory alterations, stress conditions and drug addictions, analgesia processes and neuroprotection. Mutants deficient in the Sigma-2 receptor can be used to study diagnostic or therapeutic tools to fight cancer and/or degenerative processes and/or to design compounds capable of preventing, reducing or alleviating the secondary pathology associated with administration of neuroleptic agents.
Type:
Grant
Filed:
December 9, 2003
Date of Patent:
August 23, 2011
Assignee:
Laboratorios Del Dr. Esteve, S.A.
Inventors:
Daniel Zamanillo Castanedo, Lluis Montoliu Jose, Francina Langa Vives, Alfonso Javier Lavado Judez, Victoria Eugenia Tovar Herrador
Abstract: The invention relates to novel assays for the in vivo analysis of neurodegenerative diseases and the use of such assays to discover therapies capable of modulating such diseases.
Type:
Application
Filed:
February 16, 2010
Publication date:
August 18, 2011
Inventors:
Ronald Klein, Phillip Henning, David Wang, Robert Dayton, Jason Tatom, Elysse Orchard
Abstract: The present invention relates to a transgenic non-human mammalian animal whose genome incorporates a biosensor of the activity of modulators of cell proliferation consisting of a DNA sequence that comprises the luciferase reporter transgene ligated downstream of a promoter sequence of the CYCB2 gene, this sequence promoter/reporter being flanked by HS4 insulator sequences at each of its 3? and 5? sides. The transgenic animal is proposed for the screening of compounds with pharmacologically relevant activities. The invention provides for a further use of the animal line for the study and toxicological evaluation of compounds with tumorigenic activity, and also for the study and evaluation of compounds with chemopreventive anti-cancer activity.
Type:
Application
Filed:
November 17, 2010
Publication date:
August 11, 2011
Inventors:
Adriana Maggi, Paolo Ciana, Giulia Piaggio, Frauke Goeman, Ada Sacchi, Cecilia Tiveron
Abstract: The invention provides methods and compositions for treating, ameliorating or preventing diseases or conditions caused by or aggravated by lost and/or impaired mitochondrial Complex I function, including treating, ameliorating or preventing an ischemia and/or reperfusion injury, Parkinson's disease, myopathic diseases, cardiolipin deficiency, neurodegenerative diseases, aging, diabetes, obesity, sepsis and other conditions in which mitochondrial Complex I function is lost and/or impaired.
Abstract: The technology relates to a nucleic acid expression cassette comprising a TR element encoding an mRNA molecule that is translated in stressed and/or dying cells, and a nucleotide sequence operably linked to the TR element, that is a first open reading frame (ORF) sequence and encodes a polypeptide or a fragment thereof and is co-translated with the TR element. The technology further relates to mammalian cells and a transgenic animal comprising such expression cassette.
Abstract: The invention provides compositions and methods for producing androstenedione (4-androstenedione), of improved purity and for modulating its production, for example by deletion or inactivation of ksdA, cxgA, cxgB, cxgC, or cxgD. The invention also provides methods and compositions, including nucleic acids that encode enzymes, for producing 1,4-androstadiene-3,17-dione (ADD) and related pathway compounds, including 20-(hydroxymethyl)pregna-4-en-3-one and 20-(hydroxymethyl)pregna-1,4-dien-3-one. The compositions of the invention include nucleic acids, probes, vectors, cells, transgenic plants and seeds, transgenic animals, kits and arrays.
Type:
Application
Filed:
November 13, 2008
Publication date:
August 4, 2011
Applicant:
Verenium Corporation
Inventors:
David Nunn, Catherine Pujol, Kelly Chatman
Abstract: The invention provides a new type of a capsid protein VP1 of human enterovirus 71, named as MEL701-VP1 and functional/structural variants thereof, which is used for protection against enterovirus. The transgenic animal producing the protein, the composition comprising the protein and the method for production thereof are also provided.
Abstract: The present invention provides a rodent animal for studying the molecular mechanisms and physiological processes associated with uncontrolled cell growth, e.g. cancer, and with a modified FGFR4.
Type:
Application
Filed:
September 29, 2009
Publication date:
July 21, 2011
Applicant:
MAX-PLANCK-GESELLSCHAGFT zur FOERDERUNG der WISSENSCHAFTEN e.V.
Inventors:
Axel Ullrich, Thomas Mayer, Sylvia Streit, Nina Seitzer
Abstract: Methods and compositions are presented for the administration of transposon-based vectors to an animal or human to provide gene therapy to the animal or human
Type:
Application
Filed:
November 8, 2010
Publication date:
June 30, 2011
Applicants:
College, TransGenRx, Inc.
Inventors:
Richard Cooper, Frederick M. Enright, William C. Fioretti
Abstract: A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SE The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.
Type:
Grant
Filed:
July 12, 2005
Date of Patent:
June 28, 2011
Assignee:
Van Andel Research Institute
Inventors:
George F. Vande Woude, Yu-wen Zhang, Nariyoshi Shinomiya
Abstract: The invention provides peptides and the nucleic acid sequences that encode them. The invention further provides therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders.
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.
Type:
Application
Filed:
November 10, 2010
Publication date:
June 23, 2011
Applicants:
BAXTER INTERNATIONAL INC., BAXTER HEALTHCARE S.A.
Inventors:
Johannes Oldenburg, Clemens R. Mueller-Reible, Andreas Fregin, Simone Rost, Tim-Matthias Strom
Abstract: The invention relates to cells and transgenic non-human mammals having at least one disrupted heparanase allele. The invention further relates to methods of screening therapeutic drug candidates utilizing the heparanase deficient non-human mammals and cells.
Abstract: An object of the present invention is to develop a probe for measuring in real time the kinetics of CREB or actin closely related to brain functions such as memory formation in live animals.
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 drug transport sensitivity or resistance drug transport resistance or sensitivity. 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 transporter gene such as the Slc7a11 (NC_005101.2) gene, the Abcb1 (NC_005103.2) gene, etc. The present invention also provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. 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 transporter gene.
Abstract: An anti-TrkA antibody is provided that comprises: a) a variable heavy chain comprising a sequence selected from any of BXhVH1, BXhVH2, BXhVH3, BXhVH4, BXhVH5, or HuVHWOv as shown in FIG. 1a; or from variants of any of said sequences and/or b) a variable light chain comprising a sequence selected from any of BXhVL1, BXhVL2, BXhVL3, BXhVL4, BXhVL5, BXhVL6, BXhVL7 or BXhVL8; as shown in FIG. 1b, or from variants of any of said sequences. TrkA-binding derivatives are also provided. Antibodies or derivatives of the present invention are useful in a number of therapies, including pain therapy.
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.
Type:
Grant
Filed:
September 1, 2006
Date of Patent:
May 31, 2011
Assignee:
Phylonix Pharmaceuticals, Inc.
Inventors:
Patricia McGrath, Chuenlei Parng, George N. Serbedzija
Abstract: The present invention relates to a transgenic animal, which comprises in its genome a recombinant polynucleotide encoding one or more reporter proteins and a monocyte chemotactic protein-1 (MCP-1) promoter, wherein the one or more reporter proteins are expressed under the control of the MCP-1 promoter. A method for monitoring endogenous expression of MCP-1 in vivo is also provided, which is useful for identifying a regulator of the expression of MCP-1 or an anti-inflammatory agent.
Abstract: The present invention describes methods of generating single VL domain antibodies, including chimeric single chain antibodies that comprise of a variable region of a human immunoglobulin ? or ? light chain and a non-human constant region. The non-human constant region is devoid of a first constant domain CH1, and the variable region is devoid of a heavy chain variable domain.
Abstract: The present invention relates to the use of regulatory sequences for mediating specific, early transient expression in proliferative neuronal determined cells. Furthermore, the uses of recombinant nucleic acid molecules comprising said defined regulatory sequences for mediating specific, early transient expression in proliferative neuronal determined cells as well as for the generation of non-human transgenic organisms and/or host cells are disclosed. In addition, the invention provides for transgenic non-human animals and/or host cells comprising said regulatory sequences and/or recombinant nucleic acid molecules. The invention also describes methods for the preparation of such vectors, host cells and transgenic non-human animals as well as methods for the detection and/or isolation of neuronal determined cells.
Type:
Grant
Filed:
September 12, 2008
Date of Patent:
May 24, 2011
Assignee:
F. Hoffmann-La Roche Inc.
Inventors:
Sebastien Couillard-Despres, Claudia Karl, Hans-Georg Kuhn, Ludwig Aigner
Abstract: The invention relates to a method for screening for the effects of non-genotoxic carcinogens in an animal model. The invention also relates to animal models that are suitable for use in such a method, and cell lines derived from these animals for in vitro screening purposes. More specifically, the invention relates to a transgenic rodent animal which has been humanised for the nuclear transcription factors CAR, PXR and PPAR?, and in which the endogenous equivalent genes have been rendered inoperable.
Type:
Application
Filed:
March 9, 2009
Publication date:
May 19, 2011
Applicant:
ITI SCOTLAND LIMITED
Inventors:
Charles Roland Wolf, Clifford Roy Elcombe
Abstract: Provided herein are Sirt1 polymorphic variants having a substitution at amino acid residue 107 or nucleotide 373. In certain embodiments, the Sirt1 polypeptide variants have a L107P substitution and the nucleic acid variants have a T373C substitution. Genetic and/or biochemical testing may be performed to identify whether a patient carries one of the disclosed polymorphic variants. Based on the polymorphic variant the patient carries, a medical practitioner may administer an appropriate therapy, such as a sirtuin activator.
Type:
Application
Filed:
May 15, 2009
Publication date:
May 12, 2011
Inventors:
Christoph H. Westphal, Marc Donath, Peter Elliott, Michael Jirousek, Jill Milne
Abstract: A DNA sequence containing a gene encoding a protein, the gene being under the transcriptional control in the DNA sequence of a mammalian milk protein promoter which does not naturally control the transcription of the gene, such DNA sequence including DNA enabling secretion of the protein.
Abstract: A genetically modified non-human mammal or cell characterised in that it does not comprise a nucleic acid sequence which itself encodes any endogenous immunoglobulin heavy chain constant region locus polypeptide.
Abstract: The invention provides novel polypeptides having phospholipase activity, including, e.g., phospholipase A, B, C and D activity, patatin activity, phosphatidic acid phosphatases (PAP) and/or lipid acyl hydrolase (LAH) activity, nucleic acids encoding them and antibodies that bind to them. Industrial methods, e.g., oil degumming, and products comprising use of these phospholipases are also provided.
Abstract: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.
Type:
Grant
Filed:
June 25, 2008
Date of Patent:
April 19, 2011
Assignee:
Kyowa Hakko Kirin Co., Ltd.
Inventors:
James M. Robl, Yoshimi Kuroiwa, Poothappillai Kasinathan, Isao Ishida, Kazuma Tomizuka
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.
Type:
Grant
Filed:
March 23, 2009
Date of Patent:
April 19, 2011
Assignee:
University of Kentucky Research Foundation
Abstract: Hypercellular nonhuman organisms have functionally inactivated expression of a cyclin inhibitor gene, especially p27. The growth rate of nonhuman organisms are increased such that a desired size is attained more quickly than as compared to nonvariant organisms. Inhibitors of the p27 cyclin dependent kinase inhibitor protein or sequences encoding the protein modulate vertebrate cell cycle progression and increase the proportion of dividing cells to non-dividing cells in a population of treated cells. As the proportion of dividing cells increases, the cell population, e.g., hematopoietic progenitor (stem) cells, is more efficiently used for gene therapy applications. Transgenic animals and plants, and knockout alleles are provided.
Type:
Application
Filed:
July 14, 2009
Publication date:
April 14, 2011
Applicant:
Fred Hutchinson Cancer Research Center
Inventors:
James M. Roberts, Steven R. Coats, Matthew L. Fero
Abstract: Transgenic rodents having NGF beta gene mutants in their genomes express NGF beta mutant proteins. The preparation methods of the transgenic rodents, the methods of utilizing the transgenic animals to prepare NGF beta mutant proteins and the resulting NGF beta mutant proteins are provided. The transgenic rodents are useful in preparing human NGF and in the study of the functions of NGF beta mutants and their receptors in the whole animal level, and also useful for screening and purifying NGF beta mutants which have high activity and high security.
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.
Type:
Application
Filed:
July 22, 2005
Publication date:
April 7, 2011
Applicant:
ERASMUS UNIVERSITY MEDICAL CENTER ROTTERDAM
Inventors:
Jeroen Essers, Georgios Aris Garinis, Roland Kanaar
Abstract: The present invention relates to transgenic pigs containing a dominant-negative incretin hormone receptor, namely the dominant-negative human glucose-dependent insulinotropic polypeptide receptor. The present invention furthermore relates to uses of these transgenic pigs as clinically relevant animal model systems for studying the pathogenesis and novel therapies for diabetes mellitus type 2, particularly for the maintenance and expansion of pancreatic ?-cell mass.
Abstract: Materials and methods for producing fibrinogen in transgenic non-human mammals are disclosed. DNA segments encoding A?, B? and ? chains of fibrinogen are introduced into the germ line of a non-human mammal, and the mammal or its female progeny produces milk containing fibrinogen expressed from the introduced DNA segments. Non-human mammalian embryos and transgenic non-human mammals carrying DNA segments encoding heterologous fibrinogen polypeptide chains are also disclosed.