Involving Breeding To Produce A Double Transgenic Nonhuman Animal Patents (Class 800/22)
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Patent number: 6737559Abstract: This invention relates to a see-through medaka deficient in iridophores, melanophores, xanthophores and leucophores; a see-through medaka deficient in iridophores, melanophores and xanthophores, and whose sex can be identified by the presence or absence of leucophores and/or a DNA marker; and a see-through medaka wherein a specific organ is allowed to produce luminescence by introducing a hybrid gene being a fusion of a promoter of a gene expressing specifically in that organ and a coding region of a gene encoding a fluorescent protein.Type: GrantFiled: March 22, 2001Date of Patent: May 18, 2004Inventors: Yuko Wakamatsu, Kenjiro Ozato, Minoru Tanaka, Masato Kinoshita
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Patent number: 6720472Abstract: The present invention relates to HMGI genes and proteins and methods of using the same. Embodiments of the invention pertain to methods for treating obesity, methods for treating a tumor, methods for producing a transgenic non-human mammal, methods for screening candidate compounds capable of inhibiting the biological activity of normal HMGI genes or proteins, and methods for detecting the presence of a tumor.Type: GrantFiled: January 6, 1999Date of Patent: April 13, 2004Assignee: University of Medicine and Dentistry of New JerseyInventors: Kiran K. Chada, Hena Ashar, Alex Tkachenko, Xianjin Zhou
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Patent number: 6677501Abstract: The invention provides non-human, genetically-modified mammals and genetically modified animals cells having a functionally disrupted P2×7 receptor gene. Also provided are methods for producing genetically modified mice in which one or both P2×7R alleles have been functionally inactivated.Type: GrantFiled: June 6, 2001Date of Patent: January 13, 2004Assignee: Pfizer, Inc.Inventors: Christopher A. Gabel, Beverly H. Koller
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Patent number: 6664443Abstract: Isolated nucleic acid molecules that include a tau gene sequence are described. The tau gene sequences have a mutation linked to a Tau pathology. Transgenic non-human mammals that develop a Tau pathology also are described.Type: GrantFiled: July 31, 2000Date of Patent: December 16, 2003Assignee: Mayo Foundation for Medical Education and ResearchInventors: Michael L. Hutton, Jada M. Lewis, Eileen M. McGowan
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Patent number: 6653113Abstract: The present invention provides novel methods for modifying the genome of an animal cell which typically comprise the steps of: constructing a DNA molecule in which desired sequence modifications are contained in a segment of DNA (a “targeting DNA”) that is substantially isogenic with a DNA in the cell genome (a “target DNA”); introducing the targeting DNA construct into the cell (e.g., by microinjection, electroporation, transfection, or calcium phosphate precipitation); and selecting cells in which the desired sequence modifications have been introduced into the genome via homologous recombination.Type: GrantFiled: February 19, 1999Date of Patent: November 25, 2003Assignee: Genpharm International, Inc.Inventors: Anton Berns, Els Robanus Maandag, Hein te Riele
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Patent number: 6642433Abstract: A knockout mouse in which the Fgl-2 gene has been suppressed is described. The mouse is useful in studying the role of Fgl-2 in normal and disease states including viral hepatitis, allograph rejection, fetal loss, inflammatory bowel disease, lupus glomerulonephritis; acute respiratory disease syndrome, Whipple's disease, cancer and for developing therapies to treat these diseases.Type: GrantFiled: October 13, 2000Date of Patent: November 4, 2003Assignee: Trillium Therapeutics Inc.Inventors: Gary Levy, Philip Marsden, Laisum Fung
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Patent number: 6617491Abstract: The invention provides a method for screening of plant materials as CNS stimulant/depressant using Drosophila melanogaster as a model.Type: GrantFiled: February 22, 2001Date of Patent: September 9, 2003Assignee: Council of Scientific & Industrial ResearchInventors: Abhay Sharma, Amaresh Pandey, Subhash Singh, Sushil Kumar
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Patent number: 6613957Abstract: The present invention relates to the synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitivity sites of the &bgr;-globin locus are sufficient to result in high level expression of human &agr;- or &bgr;-globin transgenes.Type: GrantFiled: September 1, 1999Date of Patent: September 2, 2003Assignee: The UAB Research FoundationInventors: Tim M. Townes, Thomas M. Ryan, Richard D. Palmiter, Ralph L. Brinster, Richard R. Behringer
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Patent number: 6605753Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.Type: GrantFiled: January 23, 2001Date of Patent: August 12, 2003Assignees: Merck & Co., Inc., McGill UniversityInventors: Brian Kennedy, Paul Payette, Michael Gresser, Chidambaram Ramachandran, Michel Tremblay, Mounib Elchebly
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Patent number: 6603058Abstract: Described is a genetically modified non-human animal model for studying the peripheral and central pathways of energy homeostasis. Also disclosed are methods of identifying compounds for regulating such pathways and a Pomc mutant mouse.Type: GrantFiled: August 12, 1999Date of Patent: August 5, 2003Assignee: Oklahoma Medical Research FoundationInventors: Miles B. Brennan, Ute Hochgeschwender
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Patent number: 6593512Abstract: A bigenic mouse is provided whose germ cells and somatic cells contain (i) inactive mouse TAU genes, and/or (ii) a transgene encoding the human TAU gene, with the transgene including all regulatory elements of the human TAU gene necessary for neuronal expression of the transgene in the bigenic mouse, and/or for human patterns of expression of the transgene in the bigenic mouse. The mice of the invention may contain one or two alleles for the human TAU gene (i.e., one or two TAU alleles). Mice of the invention are useful as a source of human Tau protein, and are useful as a model of Alzheimer's, Frontal Temporal Dementia and Parkinson's-like diseases.Type: GrantFiled: March 2, 2000Date of Patent: July 15, 2003Assignee: Cognosci, Inc.Inventors: Michael P. Vitek, Hana N. Dawson, Jeanne F. Loring
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Patent number: 6570061Abstract: Transgenic mice that produce high levels of humanized antibodies are described. Targeted gene replacement exchanges constant regions of the mouse immunoglobulin heavy and light chain genes with human genes, either through conventional gene targeting, or by use of the bacteriophage-derived Cre-loxP recombination system. The transgenic animals undergo antibody affinity maturation, and a class switch from the native immunoglobulin to the humanized form.Type: GrantFiled: February 23, 1995Date of Patent: May 27, 2003Inventors: Klaus Rajewsky, Yong-Rui Zou
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Publication number: 20030097665Abstract: The invention provides transgenic nonhuman mammals producing phosphorylated lysosomal proteins in their milk, and methods of generating the same. Phosphorylation occurs at the 6′ position of a mannose side chain residue. Also provided are methods of purifying lysosomal proteins from milk, and incorporating the proteins into pharmaceutical compositions for use in enzyme replacement therapy.Type: ApplicationFiled: March 1, 2000Publication date: May 22, 2003Inventors: Arnold J.J. Reuser, Ans T. Van der Ploeg, Frank R. Pieper, Martin Ph. Verbeet
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Patent number: 6566582Abstract: Non-human animals deficient in a function of a uridine phosphorylase gene on a chromosome, and their offspring. These non-human animals and their offspring make it possible to elucidate pathologic functions and activities of nucleic acid dysbolism and the like and also to predict utility of pyridine nucleoside antimetabolites in human, and are useful as experimental animals.Type: GrantFiled: August 8, 2001Date of Patent: May 20, 2003Assignee: Taiho Pharmaceutical Co., Ltd.Inventors: Tetsuo Noda, Hiroaki Tsujimoto, Masakazu Fukushima
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Patent number: 6563016Abstract: The invention provides a transgenic non-human animal expressing a perlecan encoding transgene. Also provided is a double-transgenic non-human animal expressing a perlecan and a amyloid encoding transgene. A method of screening for a compound which alters the rate or extent of amyloid deposition is additionally provided. The method consists of: (a) constructing a perlecan transgenic animal; (b) administering an effective amount of a test compound to said perlecan transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition. Finally, the invention provides a method of screening for a compound which alters the rate or extent of amyloid deposition. The method consists of: (a) constructing a perlecan/amyloid double-transgenic animal; (b) administering an effective amount of a test compound to said perlecan/amyloid double-transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition.Type: GrantFiled: March 27, 2000Date of Patent: May 13, 2003Assignee: University of WashingtonInventors: Alan D. Snow, Ken-Ichiro Fukuchi, John Hassell
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Patent number: 6563018Abstract: The present invention provides a gene search method comprising P-element insertion and being capable of efficiently identifying a novel gene regulating various biological functions of Drosophila and specifying a function corresponding to the novel gene. An unknown gene of Drosophila can be searched by the method comprising a step of inserting in the genome of Drosophila a gene search vector carrying two sets of an expression regulatory sequence comprising UAS sequence for GAL4 transcription factor GAL4 and a promoter sequence, as integrated in the P-element sequence in such a manner that their downstreams are in opposite directions, mating the vector-inserted Drosophila with a Drosophila expressing the GAL4 to create progeny individuals, and identifying a vector-inserted line with a phenotype different from those of wild-type Drosophila, and determining the nucleotide sequence of the gene for the mutant phenotype.Type: GrantFiled: January 14, 2000Date of Patent: May 13, 2003Assignee: Japan Science and Technology CorporationInventor: Toshiro Aigaki
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Patent number: 6541193Abstract: The invention relates to a method for screening of neuroactive drugs using the fruit fly Drosophila melanogaster, which comprises the steps of, generating a double mutant line of K+ channel genes in Drosophila melanogaster; culturing the Sh5eag1 mutant flies on Dorsophila medium under standard conditions; and anesthetizing flies with diethyl ether and observing the time taken by flies to recover from anesthesia.Type: GrantFiled: February 22, 2001Date of Patent: April 1, 2003Assignee: Council of Scientific & Industrial ResearchInventors: Abhay Sharma, Sushil Kumar
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Publication number: 20030051260Abstract: The present invention pertains to a method for treating obesity in a mammal which comprises reducing the biological activity of HMGI genes in the mammal. In another embodiment, the invention pertains to a method for treating a tumor in a patient by reducing the biological activity of normal HMGI genes which comprises administering to the patient a therapeutically effective amount of an inhibitor compound active against normal HMGI-C or HMGI(Y) genes. In another embodiment, the invention pertains to a method of producing a transgenic non-human mammal, the germ cells and somatic cells of which contain an inactivated HMGI gene sequence introduced into the mammal at an embryonic stage. In another embodiment, the invention pertains to a method for screening candidate compounds capable of inhibiting the biological activity of normal HMGI proteins. In another embodiment, the invention pertains to a method for screening candidate compounds capable of inhibiting the biological activity of normal HMGI genes.Type: ApplicationFiled: January 6, 1999Publication date: March 13, 2003Inventors: KIRAN K. CHADA, HENA ASHAR, ALEX TKACHENKO, XIANJIN ZHOU
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Patent number: 6515196Abstract: In attempts to determine the cause of hypertriglyceridemia, a model animal was established. This model is useful to analyze on the relationship between food ingestion and hypertriglyceridemia. When backcrossing of the Watanabe heritable hyperlipidemic rabbit and the Japanese white rabbit, individual rabbits with high triglyceride values were identified. A novel hereditary postprandial hypertriglyceridemic rabbit, characterized by normal serum triglyceride values under conditions of fasting and high levels of serum triglyceride value by ingestion of food was thus obtained.Type: GrantFiled: November 29, 2000Date of Patent: February 4, 2003Assignee: Yamagata UniversityInventors: Hitonobu Tomoike, Kazuo Owada, Tsunekata Ito
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Patent number: 6512161Abstract: A transgenic rabbit which has in its genomic DNA sequences that encode apolipoprotein (a) and apolipoprotein B polypeptides which are capable of combining to produce lipoprotein (a), a process for creating such a rabbit, and the use of the rabbit to identify compounds which are effective in the treatment of human diseases which are associated with, induced and/or exacerbated by Lp(a) expression.Type: GrantFiled: January 8, 1999Date of Patent: January 28, 2003Assignee: Aventis Pharmaceuticals, Inc.Inventors: Didier Rouy, Nicolas Duverger, Florence Emmanuel, Patrice Denefle, Louis-Marie Houdebine, Celine Viglietta, Edward M. Rubin, Steven D. Hughes
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Patent number: 6504080Abstract: Animal model useful for testing potential therapeutic agents for the treatment of neurodegenerative disorders, in particular disorders associated with the presence of Lewy pathology.Type: GrantFiled: October 13, 2000Date of Patent: January 7, 2003Assignee: Novartis AGInventor: Petrus Herman Maria Van Der Putten
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Publication number: 20020188961Abstract: The invention concerns the use of a non-human transgenic mammal wherein at least one of the alleles of at least one of two genes coding for endogenous insulin is made functionally inoperative with respect to the expression of insulin for determining medicines acting on pathologies involving insulin.Type: ApplicationFiled: December 7, 1999Publication date: December 12, 2002Inventors: JACQUES JAMI, DANIELLE BUCCHINI, RAJIV LOCHAN JOSHI
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Patent number: 6486381Abstract: The present invention provides mice which are deficient in the normal expression of one or more members of the RAR or RXR class of receptors, to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous or homozygous for such deficiency. The present invention further provides the use of any of the above mice and cell lines in situations where the absence of at least one RAR or RXR receptors, or the normal expression thereof, is desirable.Type: GrantFiled: October 26, 1999Date of Patent: November 26, 2002Assignees: Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite Louis Pasteur, Bristol Myers Squibb CompanyInventors: Pierre Chambon, Thomas Lufkin, David Lohnes, Manuel Mark, Andree Dierich, Philippe Gorry, Philippe Kastner, Marianne Lemeur, Cathy Mendelsohn
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Patent number: 6465714Abstract: Congenic animals and animal populations having type II diabetes-associated phenotypes are described. Insulin degradation polypeptides having amino acid substitutions linked to a type II diabetes-associated phenotypes also are described.Type: GrantFiled: November 5, 1999Date of Patent: October 15, 2002Assignee: Arexis ABInventors: L. Holger Luthman, L. G. Joakim Galli
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Patent number: 6452066Abstract: Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the &agr;:2 and &agr;:7- subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression-pattern of these genes remain largely uninvestigated. The &bgr;2-subunit is the most widely expressed neuronal nicotinic receptors subunit in the nervous system. We have studied the structural and regulatory properties of the 5′ sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative and one positive element. The positively acting sequence includes one functional E-box.Type: GrantFiled: June 6, 1995Date of Patent: September 17, 2002Assignee: Institut PasteurInventors: Jean-Pierre Changeux, Marina Picciotto, Alain Bessis
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Patent number: 6440666Abstract: The invention relates to a gene located on chromosome 1 in chickens, which in birds is involved in so called autosomal dwarfism. The most likely candidate gene has a homolog in mice and men and is called HMGI-c. The sequence of the cDNA and genomic DNA of the gene is provided, as well as uses of said sequence or parts or derivatives thereof, as well as methods of using sequences from this gene or flanking sequences, or microsatellite markers in close vicinity to this gene in methods for selecting for one of the two alleles of this gene. Specifically provided are breeding methods using discrimination between dwarf fenotypes and non dwarf fenotypes, which are a result of the allele variation within this gene.Type: GrantFiled: August 25, 1999Date of Patent: August 27, 2002Assignee: Nutreco Nederland B.V.Inventors: Martinus Antonius Mathilda Groenen, Gerardus Antonius Arnoldus Albers
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Patent number: 6414218Abstract: Nonobese Diabetic Mice (NOD mice) that do not develop diabetes may be bred to produce F1 offspring that develop a condition that closely mimics rheumatoid arthritis (RA) in humans. The RA-like disease in the F1 mice, designated NOD-RA mice, is similar to human RA in clinical, radiological, histological and serological characteristics. The parents (F0) and their progeny (F1) are not diabetic and never develop hyperglycemia, and the parental mice (F0) do not themselves exhibit any symptoms of the RA-like condition that afflicts some of their progeny. The incidence, penetrance, gender domination, progression, and lifelong exacerbation of symptoms after pregnancy shown in the RA-like condition afflicting NOD-RA mice are all comparable to phenomena observed in the human disease. The NOD-RA mice provide a new spontaneous model of human RA that will be useful for studying rheumatoid arthritis and testing new drugs and reagents for treating or diagnosing the disease.Type: GrantFiled: January 18, 2000Date of Patent: July 2, 2002Assignee: The General Hospital CorporationInventors: Denise L. Faustman, Takuma Hayashi
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Patent number: 6384298Abstract: Transgenic mice having a phenotype characterized by the substantial depletion of a mature lymphocytic cell type otherwise naturally occurring in the species from which the transgenic mouse is derived. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the lymphocytic cell type which is depleted. The transgene comprises a DNA sequence encoding a lymphatic polypeptide variant which inhibits maturation of the lymphocytic cell type.Type: GrantFiled: July 24, 1997Date of Patent: May 7, 2002Assignee: Genpharm InternationalInventors: Paulus Jacobus Angelinus Krimpenfort, Antonius Jozef Maria Berns
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Patent number: 6372958Abstract: Transgenic mice are genetically engineered for a deficiency in endoglin production. These mice may have a homozygous or hemizygous disruption of the endogenous endoglin gene. Homozygous mice exhibit a lack of endoglin production. The failure to produce endoglin results in arrested development of the vascular system of the mouse and no survival beyond E11.5. These mice and cells derived therefrom provide useful reagents for understanding the development and pathology of the mammalian vascular system.Type: GrantFiled: May 25, 2000Date of Patent: April 16, 2002Assignee: The University of Utah Research FoundationInventors: Dean Y. Li, Mark T. Keating
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Publication number: 20020032913Abstract: The present invention provides a gene search method comprising P-element insertion and being capable of efficiently identifying a novel gene regulating various biological functions of Drosophila and specifying a function corresponding to the novel gene. An unknown gene of Drosophila can be searched by the method comprising a step of inserting in the genome of Drosophila a gene search vector carrying two sets of an expression regulatory sequence comprising UAS sequence for GAL4 transcription factor GAL4 and a promoter sequence, as integrated in the P-element sequence in such a manner that their downstreams are in opposite directions, mating the vector-inserted Drosophila with a Drosophila expressing the GAL4 to create progeny individuals, and identifying a vector-inserted line with a phenotype different from those of wild-type Drosophila, and determining the nucleotide sequence of the gene for the mutant phenotype.Type: ApplicationFiled: January 14, 2000Publication date: March 14, 2002Inventor: Toshiro Aigaki
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Publication number: 20020013952Abstract: Transgenic non-human animals are described comprising a transgene for a species-specific pathogen and transgene(s) for at least one receptor restricting infection of the pathogen to the host species. Also described is a method for creating the transgenic non-human animal of this invention and a method for screening an agent for the ability to inhibit infection by a species-specific virus using said transgenic non-human animal. The transgenic animal of this invention has a sustained productive viral infection and does not develop a virus-specific immune response, thereby resulting in an extremely useful self-contained system to investigate the factors modulating in vivo replication of human pathogens, the pathophysiological effect of pathogen replication and production, and the effectiveness of novel therapies and vaccines modifying or inhibiting the course of pathogenesis.Type: ApplicationFiled: December 14, 1999Publication date: January 31, 2002Inventors: Harris Goldstein, Jessie B. Paul
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Patent number: 6331658Abstract: Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the &agr; 1→3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding &agr; 1→3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of &agr; 1→3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of &agr; 1→3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation.Type: GrantFiled: January 27, 1995Date of Patent: December 18, 2001Assignees: Integris Baptist Medical Center, Inc., Oklahoma Medical Research FoundationInventors: David K. C. Cooper, Eugen Koren
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Patent number: 6323390Abstract: A transgenic mouse, containing an oncogene or a tumor suppressor gene operably linked to a urothelium-specific promoter in its germ cells and somatic cells serves as an animal model system for human bladder cancer.Type: GrantFiled: May 22, 1998Date of Patent: November 27, 2001Assignee: New York UniversityInventors: Xue-Ru Wu, Tung-Tien Sun
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Patent number: 6316692Abstract: A composition for in vivo transfection of non-human mammalian male germ cells comprises a nucleic acid or transgene, and a gene delivery system, and optionally a protective internalizing agent, such as an endosomal lytic agent, a virus or a viral component, which is internalized by cells along with the transgene and which enhances gene transfer through the cytoplasm to the nucleus of the male germ cell. A pharmaceutical preparation and a transfer kit utilize the composition. A method for introducing a polynucleotide into non-human mammalian male germ cells comprises the administration of the composition to a non-human mammalian. A method for isolating or selecting transfected cells utilizes a reporter gene, and a method for administering transfected male germ cells utilizes male germ cells which have been transfected in vitro.Type: GrantFiled: November 13, 1998Date of Patent: November 13, 2001Inventors: Carol W. Readhead, Robert Winston
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Patent number: 6291739Abstract: The invention relates to a method for screening anti-epileptic drugs using fruit fly Drosophila melanogaster by generating single and double mutant lines of K+ channel genes in Drosophila melanogaster, culturing mutant lines on Drosophila medium under standard conditions, identifying the mutants, separating male flies under ether anesthesia, supplying the mutant males with medium containing each of the four antiepileptic drugs, phenobarbital, phenytoin, carbaamazepine and valproate, separately, administering ether anesthesia to the drug treated flies and examining their leg shaking intensity under stereomicroscope, observing the antiepileptic effect in the drug treated males wherein a reduced intensity of leg shaking, compared to leg shaking in normally fed etherized males, is indicative of antiepileptic activity in the drug.Type: GrantFiled: March 24, 2000Date of Patent: September 18, 2001Assignee: Council of Scientific and Industrial ResearchInventors: Abhay Sharma, Sushil Kumar
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Patent number: 6278040Abstract: In accordance with the present invention, there are provided targeted loss of function mutant mice which express less than endogenous levels of at least one member of the steroid/thyroid superfamily of receptors in at least one specific tissue type. For example, mutations in the RXR&agr; gene in mouse germlines are lethal in the embryonic stage between E13.5 and E16.5 when bred to homozygosity. The major defect responsible for this lethal effect is hypoplastic development of the ventricular chambers of the heart, which is manifest as a grossly thinned ventricular wall with concurrent defects in ventricular septation. This phenotype is identical to a subset of the effects of embryonic vitamin A deficiency, and therefore establishes RXR&agr; as a genetic component of the vitamin A signaling pathway in cardiac morphogenesis.Type: GrantFiled: February 19, 1997Date of Patent: August 21, 2001Assignees: The Salk Institute for Biological Studies, The Regents of the University of Calif.Inventors: Henry M. Sucov, Ronald M. Evans, Kenneth R. Chien
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Patent number: 6271436Abstract: Disclosed are methods for the isolation of primordial germ cells, culturing these cells to produce primordial germ cell-derived cell lines, methods for transforming both the primordial germ cells and the cultured cell lines, and using these transformed cells and cell lines to generate transgenic animals. The efficiency at which transgenic animals are generated by the present invention is greatly increased, thereby allowing the use of homologous recombination in producing transgenic non-rodent animal species.Type: GrantFiled: October 10, 1997Date of Patent: August 7, 2001Assignee: The Texas A & M University SystemInventors: Jorge A. Piedrahita, Fuller W. Bazer
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Patent number: 6262337Abstract: Transgenic animals containing recombinant DNA with modified nucleotide sequence from the vascular endothelial growth factor B (VEGF-B) gene, cells and methods for producing such animals, and methods of using them to assay substances for VEGF-B-like activity.Type: GrantFiled: February 18, 1998Date of Patent: July 17, 2001Assignee: Ludwig Institute for Cancer ResearchInventors: Gabriel von Euler, Karin Aase, Christer Betsholtz, Ulf Eriksson, Milos Pekny, Samuel Gebre-Medhin, Xuri Li
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Publication number: 20010008026Abstract: The present invention relates to methods and compositions for tissue-restricted gene recombination. In particular, the present invention provides methods and compositions for tissue-restricted gene recombination in post-mitotic cells. The present invention further provides methods for gene recombination in post-mitotic cells comprising the delivery of a Cre recombinase to the target tissue to facilitate recombination in a desired target nucleic acid.Type: ApplicationFiled: June 25, 1998Publication date: July 12, 2001Inventors: MICHAEL D. SCHNEIDER, PAUL OVERBEEK, PETER FRENKEL
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Patent number: 6248934Abstract: The invention provides methods and compositions for expressing targeted gene products in vertebrate neurons. The compositions include gene trap vectors comprising a polynucleotide comprising promoterless selectable marker and axon reporter encoding sequences, which may be operatively joined to an internal ribosome-entry site, and may comprise a splice acceptor site located 5′ to the selectable marker and axon reporter encoding sequences. The methods include methods of expressing an axon reporter in a cell by transferring the subject vectors into an embryonic stem cell and incubating the cell under conditions whereby the cell or a progeny of the cell differentiates into a neuron comprising an axon or dendrites, and the neuron expresses the axon reporter under the transcriptional control of the gene; and specifically detecting the axon reporter in the axon or dendrites. Neuronal specific expression may also be effected in disclosed binary systems.Type: GrantFiled: November 13, 1998Date of Patent: June 19, 2001Assignee: The Regents of the University of CaliforniaInventors: Marc Tessier-Lavigne, William C. Skarnes, Kevin Mitchell, Philip A. Leighton
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Patent number: 6245963Abstract: A genetically engineered mouse model that genotypically and phenotypically mimics human patients with spinal muscular atrophy. The genome of the mouse model contains at least one mutation that knockouts the native mouse Smn gene and at least one copy of human SMNC gene that functions in a murine background and compensates for the loss of the functions provided by the Smn gene. The phenotypes of said mouse model can be grouped according to their severity of pathological conditions into three types, paralleling the three types of human spinal muscular atrophy conditions. Said mouse model can be used for studying the pathophysiology of spinal muscular atrophy and for developing and testing existing and new therapeutic and diagnostic methods.Type: GrantFiled: May 25, 2000Date of Patent: June 12, 2001Assignee: Academia SinicaInventors: Hung Li, Hsiu-Mei Hsieh-Li, Jan-Gowth Chang
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Patent number: 6245964Abstract: The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.Type: GrantFiled: December 10, 1998Date of Patent: June 12, 2001Assignee: Elan Pharmaceuticals, Inc.Inventors: Lisa C. McLonlogue, Jun Zhao, Sukanto Sinha
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Patent number: 6245966Abstract: The present application shows that the expression of Coxsackievirus and/or Adenovirus (CAR) in various lymphocyte cell lines is sufficient to facilitate the efficient transduction of these cells by adenoviruses. This property of CAR does not require its cytoplasmic domain. Use of a truncated CAR (tCAR) lacking the cytoplasmic domain has the unexpected advantage in that integrin expression is not increased in lymphocytes expressing tCAR, whereas lymphocytes expressing full-length CAR exhibit upregulated integrin expression. Further provided are transgenic mice which have been genetically engineered for tissue-specific (lymphocyte) expression of tCAR.Type: GrantFiled: March 19, 1999Date of Patent: June 12, 2001Assignee: University Technology CorporationInventor: James DeGregori
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Patent number: 6218597Abstract: The invention provides a transgenic mouse that is a model for heart muscle disease and heart failure. Also provided are methods of using the transgenic mouse model to study heart muscle disease and heart failure and conditions and treatments related thereto.Type: GrantFiled: April 1, 1998Date of Patent: April 17, 2001Assignee: University Technology CorporationInventors: J. David Port, Michael R. Bristow
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Patent number: 6207876Abstract: The present invention relates to the production of adenosine deaminase (ADA) deficient mice and the use of such mice as an animal model for dysfunctions associated with elevated adenosine levels. Also, provided by the present invention are methods of treating dysfunctions associated with elevated adenosine levels and methods of screening compounds for pharmaceutical activity in the treatment of dysfunctions associated with elevated adenosine levels.Type: GrantFiled: April 28, 1999Date of Patent: March 27, 2001Assignee: Board of Regents, The University of Texas SystemInventors: Rodney E. Kellems, Surjit K. Datta, Michael R. Blackburn
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Patent number: 6187993Abstract: A nucleic acid construct comprising a promoter capable of directing expression in the suprabasal cells of the epidermis and means to cause expression of an integrin subunit in the suprabasal cells. Preferably the means to cause expression of an integrin subunit is an integrin subunit coding sequence. A transgenic animal which expresses an &agr; subunit and a &bgr; subunit of integrin in the suprabasal cells of the epidermis and methods for making the transgenic animals. At least some of the transgenic animals are useful models of human disease, especially psoriasis. A method of treating psoriasis comprising administering to the patient a compound which modulates integrin function.Type: GrantFiled: November 3, 1997Date of Patent: February 13, 2001Assignee: Imperial Cancer Research Technology LimitedInventors: Fiona M. Watt, Joseph M. Carroll
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Patent number: 6172278Abstract: Transgenic cells, transgenic mice having an Ikaros transgene and methods for the use thereof.Type: GrantFiled: July 29, 1994Date of Patent: January 9, 2001Assignee: The General Hospital CorporationInventor: Katia Georgopoulos
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Patent number: 6166288Abstract: A method of xenotransplanting organs, tissues, cells or non-viable components which reduces or prevents antibody-mediated rejections, including hyperacute rejection, is provided wherein transgenic animals are produced that express at least one enzyme which masks or reduces the level of the antigenic Gal.alpha.(1,3)Gal or gal epitope, and at least one complement inhibitor such as CD59, DAF and/or MCP. The transgenic animals which express both a gal epitope-reducing enzyme and a complement inhibitor will have masked or reduced levels of the gal epitope and will be much less likely to produce an antibody-mediated rejection following transplantation, and the expression of the complement inhibitor will also suppress complement activation and reduce even further a severe immune reaction following the transplantation of donor organs, tissue, cells or non-viable components from the transgenic animals so produced.Type: GrantFiled: July 3, 1996Date of Patent: December 26, 2000Assignee: Nextran Inc.Inventors: Lisa E. Diamond, John S. Logan, Geurard W. Byrne, Ajay Sharma
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Patent number: 6162963Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.Type: GrantFiled: June 5, 1995Date of Patent: December 19, 2000Assignee: Abgenix, Inc.Inventors: Raju Kucherlapati, Aya Jakobovits, Sue Klapholz, Daniel G. Brenner, Daniel J. Capon
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Patent number: 6127598Abstract: The present invention features mouse models for Nkx-2.2 gene function and for Nkx-6.1 gene function, wherein the transgenic mouse is characterized by having a defect in Nkx-2.2 gene function or a defect in Nkx-6.1 gene function (where, because Nkx-2.2 acts upstream of Nkx-6.1, a defect in Nkx-2.2 gene function affects Nkx-6.1 gene function) and by having a decreased number of insulin-producing cells relative to a normal mouse. Where the transgenic mouse contains a defect in Nkx-2.2 gene function, the mouse is further characterized by a decreased number of serotonin-producing cells relative to a normal mouse. The transgenic mice may be either homozygous or heterozygous for the Nkx-2.2 or Nkx-6.1 defect.Type: GrantFiled: July 25, 1997Date of Patent: October 3, 2000Assignee: The Regents of the University of CaliforniaInventors: Michael S. German, John L.R. Rubenstein, Lori Sussel, Maike Sander, Dennis J. Hartigan-O'Connor, Roger A. Pedersen, Juanito J. Meneses