Abstract: The present disclosure provides herein anti-CD4 antibodies or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.

Abstract: The invention described herein provides non-HLA matched humanized mouse model (e.g., NSG mouse model) with patient-derived xenograft (PDX), as well as methods of making and using the same.

Abstract: Provided are methods of producing an isolated T memory stem cell population, the method comprising a) isolating nave T cells from a mammal, wherein the mammal is not a mouse; b) activating the nave T cells and expanding the numbers of nave T cells in the presence of one or more non-specific T cell stimuli, one or more cytokines, and a GSK-3beta inhibitor. Also provided are methods of producing an isolated T memory stem cell population, the method comprising a) isolating lymphocytes from a mammal; b) sorting the lymphocytes using flow cytometry into a population comprising a phenotype comprising i) CD95+, CD45RO?, and CCR7+; and ii) CD62L+ or one or more of CD27+, CD28+, CD45RA+, and CD127+ to produce an isolated T memory stem cell population. Further embodiments of the invention provide related cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Abstract: Methods for producing stem cell banks, preferably human, which optionally may be transgenic, e.g., comprised of homozygous MHC allele cell lines are provided. These cells are produced preferably from parthenogenic, IVF, or same-species or cross-species nuclear transfer embryos or by dedifferentiation of somatic cells by cytoplasm transfer. Methods for using these stem cell banks for producing stem and differentiated cells for therapy, especially acute therapies, and for screening for drugs for disease treatment are also provided.

Abstract: A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Abstract: The invention relates to a non-human primate animal model for HBV infection, said animal model being of the Cercopithecidae family.

Abstract: Described herein are immunodeficient non-human animals lacking expression of toll-like receptor 4 (TLR4) by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient non-human animal lacking expression of toll-like receptor 4 (TLR4), thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells. Further described are immunodeficient mice lacking expression of toll-like receptor 4 by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient mouse lacking expression of toll-like receptor 4, thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells.

Abstract: The present invention relates to a transgenic animal model system based on the development of transgenic mice bearing components of the human immune system. Specifically, the invention relates to a Flk2 deficient Rag?/??c?/? transgenic mouse and the engraftment of said mouse with human hematopoietic stem cells. The present invention further provides methods for increasing the numbers of functionally competent human dendritic cells and the hematopoietic targets cells that they interact with in said transgenic mouse through the administration of Flk2L. The transgenic animal model system of the invention may be used for testing human vaccine candidates, for screening potential immune adjuvants and for developing novel therapeutics.

Abstract: The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

Abstract: The invention provides an animal model and methods of generating large numbers of diverse, functional, naïve T cells in mice using bone marrow cells from adult donors.

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

Abstract: The present invention relates to the use of a Severe Combined T-B-Immune Deficient (SCID) mouse engrafted with human immunocompetent cells (Hu-SCID-mouse) as an animal model for the evaluation of the effectiveness of an HIV vaccine. Furthermore, the present invention relates to a method for the evaluation of an HIV vaccine, wherein a Hu-SCID-mouse of the invention is inoculated with the HIV vaccine and thereafter challenged with HI-virus. The invention also relates to novel HIV vaccine compositions, which can be evaluated using the animal model.

Abstract: The invention provides methods and compositions for screening candidate compounds for activity in altering the level of expression of Schlafen (Slfn) in cells, tissues and animals. The invention also provides methods and compositions for screening candidate compounds for activity in altering the level of virus infection. The invention further provides methods and compositions for screening candidate compounds for altering the level of expression of virus proteins without substantially unfaltering the level of expression of cellular proteins. The invention additionally provides methods and compositions for diagnosing the risk and/or susceptibility to virus infection. The invention also provides transgenic non-human animals, and transgenic cells, comprising a mutant Schlafen (Slfn) gene, such as a knockout mutation. These invention's compositions and methods are useful as models for virus infection, and for screening candidate prophylactic and/or therapeutic anti-viral compounds.

Abstract: Porcine animals, tissue and organs as well as cells and cell lines derived from such animals are provided that lack functional endogenous immunoglobulin loci and are deficient in immunoglobulin expression and B-cells. These animals are useful as model systems for research and for development of new pharmaceutical and biological agents. In addition, methods are provided to prepare such animals.

Abstract: 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.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO194, PRO220, PRO241, PRO284, PRO331, PRO354, PRO355, PRO533, PRO541, PRO725, PRO937, PRO1014, PRO1120, PRO1182, PRO1325, PRO1382, PRO1410, PRO1555, PRO1556, PRO1760, PRO1787, PRO1868, PRO4326, PRO4332, PRO4346, PRO4400, PRO6003, PRO6094, PRO6244, PRO9820, PRO9828, PRO10274, PRO16090, PRO19644, PRO21340, PRO92165, PRO85143, PRO1124, PRO1026 or PRO23370 genes.

Abstract: 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.

Abstract: HIV does not cause disease in any non-human species. Thus, there is no animal model system to evaluate the efficacy of strategies aimed at preventing, treating or curing disease caused by this virus. The present invention provides compositions and a method for producing an animal model for HIV induced disease. The present invention is an animal adapted to simulate a human-like immune response to HIV, which is accomplished by activation and inactivation of complement of proteins within the animal. Accordingly, the present invention stages certain human proteins within an animal by way of its gut associated lymphoid tissue followed by infection of live HIV.

Abstract: The present invention relates to the use of a GPR4 inhibitor for the manufacture of a medicament for the inhibition of angiogenesis, for instance for the inhibition of tumour growth in the treatment of cancer. In a preferred embodiment, said inhibitor is a siRNA, preferably double-stranded. In addition, the present invention further encompasses non-human animals wherein the GPR4 has been inactivated, for instance a knock-out mouse lacking GPR4, and the use of said animals as an experimental model for angiogenesis and for screening for compounds modulating angiogenesis.

Abstract: The teachings are directed to an immunocompetent xenograft model. The model comprises an immunodeficient animal modified to have a reconstituted immune system, wherein a xenograft is transplanted in the animal and allowed to establish for an establishment period of at least about 10 days. The xenograft simulates a tissue in a subject in need of a treatment. In these embodiments, the reconstituted immune system is created after the establishment period, and is created by administering a total number of T-cells to the animal. The total number of T-cells consists of a preselected number of responsive T-cells, a preselected number of non-responsive T-cells, and a preselected ratio of responsive T-cells to total T-cells. The preselected number of responsive T-cells simulates a number of responsive T-cells in the subject, and the ratio of the number of responsive T-cells to total T-cells ranges from about 1:100,000 to about 30:100,000.

Abstract: It is intended to disclose the function of dendritic cell immunoreceptor (DCIR) and clarify its role in the onset of autoimmune arthritis. It is also intended to provide a method of screening a substance which is useful in treating/preventing an autoimmune disease or osteoporosis. A nonhuman disease model animal characterized by having a partial or entire deficiency of a gene encoding the DCIR protein on the chromosome; a method of screening a substance which is useful in treating/preventing a DCIR-related disease, for example, an autoimmune disease such as arthropathy by using the nonhuman disease model animal as described above; and a remedy/preventive therefor.

Abstract: The invention relates to non-peptidic molecules which modulate, especially inhibit, the interaction of protein kinase A (PKA) and A kinase anchor proteins (AKAP) and to a host or target organism that comprises said non-peptidic compounds or recognition molecules directed to said compounds, such as e.g. antibodies or chelating agents. The invention also relates to a pharmaceutical agent, especially for use in the treatment of diseases that are associated with a disturbance of the cAMP signal path, especially insipid diabetes, hypertonia, pancreatic diabetes, duodenal ulcer, asthma, heart failure, obesity, AIDS, edema, hepatic cirrhosis, schizophrenia and others. The invention also relates to the use of the inventive molecules.

Abstract: 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.

Abstract: Contemplated compositions and methods are directed to prevent and/or treat various autoimmune diseases that are typically associated with glycan dysregulation, and especially autoimmune demyelinating diseases. Further especially contemplated aspects include animal models and systems for screening compounds to treat and/or prevent such diseases.

Abstract: A transgenic mouse is disclosed herein whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor. A mouse homozygous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function. A method is disclosed for altering a B cell activity. The method includes administering a therapeutically effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity. A method is also disclosed for of treating a subject with Job's disorder or atopic disease. A method is also disclosed for treating or preventing an allergic reaction in a subject. A method is also disclosed for treating a subject with an autoimmune or antibody mediated disorder.

Abstract: HIV does not cause disease in any non-human species. Thus, there is no animal model system to evaluate the efficacy of strategies aimed at preventing, treating or curing disease caused by this virus. The present invention provides compositions and a method for producing an animal model for HIV induced disease. The present invention is an animal adapted to simulate a human-like immune response to HIV, which is accomplished by activation and inactivation of complement of proteins within the animal. Accordingly, the present invention stages certain human proteins within an animal by way of its gut associated lymphoid tissue followed by infection of live HIV.

Abstract: There is discloses a transgenic mouse over-expressing a potassium channel BEC1, which can be used as an effective tool for screening a substance for antidementia or a substance to improve learning and memory.

Abstract: The application discloses novel polypeptides and nucleic acids involved in a variety of biological processes, including viral reproduction. Related methods and compositions are also described.

Abstract: The invention provides transgenic animals comprising a lentiviral transgene, such as an HIV transgene. Also within the scope of the invention are cells and eggs from the transgenic animal. Further included are methods for identifying therapeutic compounds for preventing lentiviral infection and treating associated disease (e.g. AIDS).

Abstract: The invention provides constructs that feature a nucleic acid molecule encoding an amino terminal region of a BRI polypeptide. A construct of the invention can further include a multiple cloning site joined to the 3′ end of the BRI nucleic acid molecule or a nucleic acid molecule encoding a heterologous polypeptide operably linked to the BRI nucleic acid molecule. The invention further provides methods of directing a heterologous polypeptide through the secretory pathway in a cell. Such methods utilize a construct of the invention that additionally contains a promoter that directs expression of the BRI and heterologous nucleic acid molecules. The construct is introduced into a cell and, following expression, the fusion protein is directed through the secretory pathway of the cell. In addition, a construct of the invention can be introduced into an animal to make the animal transgenic for the heterologous polypeptide.

Abstract: The present invention provides a method for developing a human T cell-engrafted mouse, which includes transplanting a human-derived bone tissue into an inbred line mouse deficient in immune cells, and a human T cell-engrafted mouse obtainable by the method. The present invention also provides a method for preparing an HIV-infected mouse model, which includes infecting the human T cell-engrafted mouse with HIV, and an HIV-infected mouse model obtainable by the method.

Abstract: Functional chimeric proteins that comprise HIV Gag protein and a Gag protein of non HIV origin (e.g., of viral or retroviral origin other than HIV origin) and overcome the block to HIV assembly in non human cells. One embodiment of the present invention is chimeras between HIV Gag protein and a Gag protein from a murine virus, such as Moloney Murine Leukemia Virus (MLV) Gag protein, that overcome the block to HIV assembly in mouse cells.

Abstract: The present invention relates to a non-human transgenic mouse containing a constitutively active G-protein coupled receptor, which produces Kaposi's sarcoma-like symptoms. The transgenic mouse is useful in identification of reagents for the prevention, treatment and/or cure of diseases related to production of proliferative vascular lesions, including Kaposi's sarcoma.

Abstract: This invention provides novel animal models for a human pathogen that is capable of exhibiting analogous secondary disease manifestation. Other animal models for a human pathogen are provided by this invention which are capable of exhibiting analogous secondary disease manifestations and are also capable of responding to therapeutic or preventive measures to such secondary disease manifestations. Other animal models for human retrovirus infections are provided including lower primates and primate excluding any members of the order Anthropoidea. Compositions, drugs, products and procedures for therapeutic and diagnostic applications derived from the animal models of this invention are also described and provided.

Abstract: Methods and compositions are provided for the creation and screening of non-human animal models having chronic inflammation. Immunocompromised host animals are injected with a population of immunocompetent effector cells, depleted of CD25+ T cells. The effector cells are tolerant of the host major histocompatibility antigens, but reactive to at least one antigen present in the host animal. The transferred cells are preferably stimulated and localized by administration of an immunostimulant at a local site. The animals are useful for a variety of screening assays and for investigation into disease causes and pathways. A variety of chronic inflammatory diseases may be studied with this model, including psoriasis, rheumatoid arthritis, diabetes, inflammatory bowel disease and multiple sclerosis.

Abstract: 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.

Abstract: The present invention provides a method for developing a human T cell-engrafted mouse, which includes transplanting a human-derived bone tissue into an inbred line mouse deficient in immune cells, and a human T cell-engrafted mouse obtainable by the method. The present invention also provides a method for preparing an HIV-infected mouse model, which includes infecting the human T cell-engrafted mouse with HIV, and an HIV-infected mouse model obtainable by the method.

Abstract: Immunocompromised mammalian hosts are sub-cutaneously implanted with a combination of human fetal bone and spleen. The chimeric animals can produce human B-cells, myeloid cells and T-cells for up to 9 months in vivo when supplied with an allogeneic human fetal thymic fragment at the same site. Grafts contain cell populations expressing CD4 and CD8, CD19 or CD33, CD14 and CD15, all of which also express the HLA type of the fetal bone/spleen. T-cells derived from progenitors in the fetal bone/spleen contain both mature single positive CD4+CD8−, CD8+CD4− as well as a high percentage of immature double positive CD4+CD8+ populations.

Abstract: A model of systemic mold/Aspergillus infection in a profoundly immunocompromised host has been established in the beagle dog. The beagle was rendered immunosuppressed using a combination of total body irradiation and daily steroids, which provided a window of time where the mold could be successfully inoculated through a bronchoscope. This created a localized infection in one lung lobe, which subsequently spread diffusely throughout the lung parenchyma, and uniformly resulted in the animal's death. The invention contemplates the further study of the pathophysiology of opportunistic mold infections in vivo and also provides examples for the development of new antifungal agents and more effective combinations of agents. Finally, the invention contemplates the development of technology for the early detection of systemic mold infections.

Abstract: 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.

Abstract: 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.

Abstract: The invention relates to an atrichia mouse which grows juvenile hair but is deficient in the ability to grow pelage hair and, more particularly, to an atrichia mouse such that the spontaneous prevalence of wet and dry skin lesions is not less than 70%. at the 24th week of age, the number of mast cells in the skin is not less than about 50/linear mm at the 24th week of age, and the serum IgE level is not less than about 3500 ng/ml at the 24th week of age. The atrichia mouse of the invention finds application as an animal model of disease for the research and development of therapeutic drugs for dermatitis, among other kinds of drugs.

Abstract: Immunocompromised or immunosuppressed non-primate chimeric mammalian hosts comprising a neuronal graft in the eye are provided for studying various events associated with humans. Particularly, the chimeric host may have solely human fetal neuronal xenografts or other fetal xenografts with other tissue, where the various tissues may be studied as to their response to a variety of agents, their response to pathogens or other diseased states, or their response to agents for the treatment of the various indications.

Abstract: This invention provides useful solid chimeric organs as well as animal models having such solid chimeric organs and processes for their preparation. Such organs find significant value and use in developing new models for disease, drug and therapeutic investigations and monitoring, and in studying storage functions and processes. The solid chimeric organs are comprised of recipient cells and donor cells, the latter themselves comprising allogeneic or xenogeneic cells which are unmodified or modified to contain one or more nucleic acid segments capable of exhibiting at least one biological property, e.g. DNA synthesis, replication, promoter function, transcription, translation, reverse transcription, and the like, non-native to the donor cell. The solid chimeric organs can be prepared from recipient organs using recipient cells and implanted allogeneic or xenogeneic donor cells from non-homologous organs or tissues.

Abstract: The present invention provides animals and methods for the evaluation of vaccines. In particular, the present invention provides humanized animal models for the evaluation of vaccines designed to confer immunity against human pathogens, including vaccines directed against the human immunodeficiency virus. The present invention further relates to HIV vaccines. In particular, the present invention provides attenuated replication-competent HIV vaccines and replication-defective HIV vaccines. In addition, the invention provides modified Leishmania cells expressing HIV proteins.

Abstract: A specific method has been developed to produce an autoimmune response and resulting clinical symptoms for a particular disease process. Peptides or other structures derived from an autoantigen and which are bound by auto antibody or T cell receptors are identified and used to induce an immune response. This immune response evolves into an autoimmune response directed against the other portions of the protein from which the peptide was derived. Subsequently, clinical manifestations may appear that are also found in the clinical illness. selected from the group including viruses, bacteria, fungi, parasites, rickettsia, plasmids, and insects which contains a structure or a peptide sequence that is similar to a structure or peptide sequence that has been identified by the method of claim 1 to the extent that it is bound by one of the group selected from antigen specific B cell surface receptors, and antigen specific T cell receptors.

Abstract: Transgenic cells, transgenic mice having an Ikaros transgene and methods for the use thereof.

Abstract: The invention provides transgenic animals comprising a lentiviral transgene, such as an HIV transgene. Also within the scope of the invention are cells and eggs from the transgenic animal. Further included are methods for identifying therapeutic compounds for preventing lentiviral infection and treating associated disease (e.g. AIDS).

Abstract: The present invention provides a non-human genetically immunodeficient mammal the peripheral blood of which contains a non-lethal percent of T-cells of human origin which is at least 20% as well as a non-human genetically immunodeficient mammal having a lethal percent of T-cells of human origin in the peripheral blood which is at least 60%. Also provided is a method of screening a substance for anti-HIV activity comprising obtaining a non-human genetically immunodeficient mammal having a lethal percent of human T-cells in the peripheral blood which is at least 60%; infecting the mammal with an amount of HIV sufficient to rescue the mammal from death from the effects of the lethal percent of human T-cells; administering the substance to the mammal; and determining if the substance kills the mammal by inhibiting the rescue of the mammal by HIV, the death of the mammal indicating a substance having anti-HIV activity.

Abstract: This invention is directed to a chimeric mouse capable of mounting murine cellular and humoral immune response, where the chimeric mouse is tolerant of human tissue implanted therein. The chimeric mouse of this invention is capable of developing murine T cells and producing murine IgG antibodies, which T cells and antibodies are tolerant of the human tissue implanted in the mouse. This allows for the challenge of the vaccinated mouse with human-specific pathogens and determining the capacity of the vaccine to protect the cells in the implanted tissue from infection. This invention is also directed to a method for the development of the chimeric mouse, as well as to the use of the chimeric mouse for the screening of vaccines for human-specific pathogens.