Abstract: Mammals and myocardial mammal cells transformed with G protein coupled receptor EDG2 are presented for use in an animal model for heart failure.

Abstract: The present invention provides an isolated mammalian adenosine receptor, isolated or recombinant nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods of making the receptor using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the receptor and are useful for treating medical conditions caused or mediated by adenosine. Also provided are screening methods for identifying specific agonists and antagonists of the mammalian adenosine receptor.

Abstract: Rat secreted embryonic alkaline phosphatase and methods for it use are provided.

Abstract: Fluorescent indicators including a binding protein moiety, a donor fluorescent protein moiety, and an acceptor fluorescent protein moiety are described. The binding protein moiety has an analyte-binding region which binds an analyte and causes the indicator to change conformation upon exposure to the analyte. The donor moiety and the acceptor moiety change position relative to each other when the analyte binds to the analyte-binding region. The donor moiety and the acceptor moiety exhibit fluorescence resonance energy transfer when the donor moiety is excited and the distance between the donor moiety and the acceptor moiety is small. The indicators can be used to measure analyte concentrations in samples, such as calcium ion concentrations in cells.

Abstract: Highly purified hepatic stem cells are trans-differentiated into pancreatic endocrine hormone-producing cells by culturing them in vitro in a medium containing high levels of glucose. These trans-differentiated cells express insulin, glucagon, and pancreatic polypeptide, but not hepatocyte protein Hep-par. When stimulated with glucose, these cells synthesize and secrete insulin, a response enhanced by nicotinamide. Transplantation of these trans-differentiated cells into a hyperglycemic animal normalizes blood sugar levels in the animal.

Abstract: The amount of active Robo expressed on a cell is modified by modulating the effective amount of a Comm polypeptide in contact with the cell, whereby the amount of expressed active Robo is modulated inversely with the modulation of the effective amount of the Comm polypeptide in contact with the cell. In a particular embodiment, the Comm polypeptide is provided to the cell by exogenously in a pharmaceutically acceptable composition. In another aspect, the invention provides methods of screening for agents which modulate Robo-Comm interactions. These methods generally involve forming a mixture of a Robo-expressing cell, a Comm polypeptide and a candidate agent, and determining the effect of the agent on the amount of Robo expressed by the cell.

Abstract: Current sources of neural stem and progenitor cells for neural transplantation are essentially inaccessible in living animals. This invention relates to neural precursor cells (stem cells, progenitor cells or a combination of both types of cells) isolated from the olfactory epithelium of mammals that can be passaged and expanded, and that will differentiate into cell types of the central nervous system (CNS), including astrocytes, oligodendrocytes, and tyrosine-hydroxylase-positive neurons. These precursor cells provide an accessible source for autologous transplantation in CNS, PNS, spinal cord and other damaged tissues.

Abstract: Monoclonal antibodies having high affinity for N-terminus pro brain natriuretic peptide (NT-proBNP) are described. The monoclonal antibodies are prepared against a synthetic peptide having the Sequence ID No. 1. Specifically, the monoclonal antibodies described are produced from two hybridoma cell lines, 6G11-F11-D12 and 1C3-E11-R9, deposited with the American Type Culture Collection under Accession Numbers PTA-4844 and PTA-4845 respectively. The monoclonal antibody antibodies can be used as reagents in an immunoassay system to identify blood, serum or plasma levels of NT-proBNP. Such an immunoassay system can be used for diagnosing and quantifying congestive heart failure (CHF).

Abstract: The present invention relates to the field of DNA recombinant technology. More specifically, this invention relates to fusion proteins comprising an ATP generating polypeptide joined to a polypeptide that converts ATP into a detectable entity. Accordingly, this invention focuses on sulfurylase-luciferase fusion proteins. This invention also relates to pharmaceutical compositions containing the fusion proteins and methods for using them.

Abstract: The invention relates to the use of a secretor variant cell-line expressing the alpha moiety of human IgE binding protein to determine the allergic status of a given individual. Moreover, the cell-line is also used to provide an assay system for determining the allergenicity of substances and for subsequently providing therapeutic compositions which render said substances ineffective. In addition, the invention also relates to the use of said cell-line to determine the IgE independent irritancy of substances and compositions effective for attenuating the effects of said substances.

Abstract: The invention provides an essentially pure preparation of human adult astrocytes, and a method of producing same. The purified astrocytes are useful for the treatment of neurodegenerative disorders or trauma to the central nervous system.

Abstract: Nucleic acid molecules encoding vertebrate telomerase are provided. Gene products, expression vectors and host cells suitable for expressing telomerase are also provided. Methods for identifying inhibitors of telomerase activity and inhibitor compositions are disclosed.

Abstract: A process for generating multipotent cells from glial cells using in vitro techniques to dedifferentiate fetal or adult mammalian glial cells into multipotent cells. The multipotent cells may further be differentiated into particular types of nervous system cells, including neurons, astrocytes, and oligodendrocytes. A small sample of astrocytes is used to establish an in vitro culture of cells that is expanded and processed to yield multipotent cells that may be used directly or be differentiated to yield neurons and/or oligodendrocytes and/or astrocytes. The invention includes implanting the generated cells into patients. The invention includes a step of exposing the cells to a growth factor.

Abstract: The invention features retina-derived (retinal endothelial or retinal epithelial pigment) cell lines with extended life-span and capable of being implanted in the retina and of carrying a therapeutic substance to the eye and to the central nervous system. Such lines can also be used as a model for studying blood central nervous system interfaces. These lines are derived from primary retinal cultures selected from the group consisting of primary retinal endothelial cells and primary retinal epithelial cells, comprise a polynucleotide containing an oncogene, which polynucleotide is optionally associated with at least one selection gene, and have the morphological characteristics and at least the expression characteristics of the surface antigens of corresponding primary cultures.

Abstract: Conditionally-immortalized PNS progenitor cell lines are provided. Such cell lines, which may be clonal, may be used to generate neurons. The cell lines and/or differentiated cells may be used for the development of therapeutic agents to prevent and treat a variety of PNS-related diseases. The cell lines and/or differentiated cells may also be used in assays and for the general study of PNS cell development, death and abnormalities.

Abstract: The present invention concerns methods for the ex vivo formation of mammalian bone and subsequent uses of the bone. A critical and distinguishing feature of the present invention are defined tissue culture conditions and factors resulting in the formation of bone cell spheroids. The invention also provides for methods of implanting into subjects the ex vivo formed bone. Also described are methods for genetically altering the bone cell spheroids to affect bone formation, identification of candidate modulators of bone formation, and identification of genes involved in bone formation.

Abstract: Congenic rats are disclosed which express a truncated form of GPR10, wherein the truncation is the first 64 amino acids present in the NH2-terminus of wild-type GPR10. Also disclosed are in vitro screening methods for identifying compounds that bind to or modulate the function or expression of the truncated GPR10, and thus are useful in treating psychiatric diseases, such as depression and anxiety.

Abstract: The present invention provides a model for studying the development of, and/or pathologies associated with neurodegenerative diseases, and agents that can alter such development and/or pathologies. The model of the invention is especially useful as an Alzheimer's disease model. The model of the invention provides brain cells and a method for increasing neurodegenerative disease characteristics in such cells, especially, induction of neurofibrillary tangles and/or phosphorylated tau and/or tau fragments and/or the production and/or release of cytokines and/or microglia reactions and/or activations and/or inflammation and/or conversion of p35 to p25 and/or the levels and activities of protein kinases by selectively increasing the concentration of cathepsin D to an effective level, and/or by lowering the concentration of cholesterol in such cells.

Abstract: The present invention discloses a PC12 cell line stably expressing human A53T &agr;-synuclein, wherein a cell of the cell line is characterized by proteasomal dysfunction, dopaminergic dysfunction, lysosomal dysfunction, and increased non-apoptotic cell death, as compared to cells of suitable control cell line not expressing mutant &agr;-synuclein. Also provided are methods of making the cells of the present invention. The unique phenotype associated with the cells described herein provide a cellular model for the study of Parkinson's Disease, as well as for other synucleinopathic neurodegenerative disorders, including, but not limited to, Dementia with Lewy Bodies, Lewy Body Variant of Alzheimer's Disease, Multiple System Atrophy and Hallervorden-Spatz syndrome.

Abstract: This invention relates to novel potassium channels and genes encoding these channels. More specifically the invention provides isolated polynucleotides encoding the KCNQ5 potassium channel subunit, cells transformed with these polynucleotides, transgenic animals comprising genetic mutations, and the use of the transformed cells and the transgenic animals for the in vitro and in vivo screening of chemical compounds affecting KCNQ5 subunit containing potassium channels.

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: Bone marrow cells are induced to differentiate into pancreatic hormone-producing cells in vitro and to repopulate a pancreas in vivo. These insulin-producing cells can be used to regenerate a damaged pancreas and reverse hyperglycemia in mammals.

Abstract: Mammals and myocardial mammal cells transformed with G protein coupled receptor EDG2 are presented for use in an animal model for heart failure.

Abstract: Isolated CHF, isolated DNA encoding CHF, and recombinant or synthetic methods of preparing CHF are disclosed. These CHF molecules are shown to influence hypertrophic activity and neurological activity. Accordingly, these compounds or their antagonists may be used for treatment of heart failure, arrhythmic disorders, inotropic disorders, and neurological disorders.

Abstract: The present invention relates generally to mammalian multipotent adult stem cells (MASC), and more specifically to methods for obtaining, maintaining and differentiating MASC to cells of multiple tissue types. Uses of MASC in the therapeutic treatment of disease are also provided.

Abstract: The invention relates to a system for selecting differentiating embryonic or adult stem cells or embryonic germline cells in a cell-specific and development-specific manner, using a combination of resistance genes and detectable reporter genes under the common control of a cell-specific and/or development-specific promoter.

Abstract: The present invention makes available powerful tools for the study of cancer, based on a novel expression construct for a constitutively active hydrocarbon receptor CA-AhR. The invention further comprises transgenic non-human animals, preferably mammals, expressing CA-AhR in one or more tissues thereof. An animal model based on the transgenic non-human animals forms the basis for novel methods e.g. for the study of cancer; for the screening of compounds, such as drug candidates; for the investigation of the molecular mechanisms of cancer, in particular stomach cancer; for the investigation of the mechanisms of highly differentiated adenocarcinoma etc. Likewise, in vitro models based on transformed cells or cell lines, functionally incorporating the inventive construct are disclosed.

Abstract: A transgenic rat containing in its genome a nucleotide sequence encoding a Ga subunit protein, which Ga protein subunit is uncoupled from regulation by Regulators of G-Protein Signaling (RGS) proteins, which Gx subunit protein is eventually the dominant-negative G188S mutant of Gax9, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic rat expresses the GA subunit protein in neural cells resulting in extended D-protein coupled receptor signaling mediated by the Ga subunit protein.

Abstract: The present invention relates to nucleic acid molecules encoding expression products involved in the Responder function, which contributes to the phenomenon of transmission ratio distortion. The present invention also relates to regulatory regions of the genes corresponding to said nucleic acid molecules. The present invention further relates to recombinant DNA molecules and vectors comprising said nucleic acid molecules and/or regulatory regions as well as to host cells transformed therewith. Additionally, the present invention relates to transgenic animals, comprising said nucleic acid molecules, recombinant DNA molecules or vectors stably integrated into their genome. The various embodiments of the invention have a significant impact on breeding strategies by allowing for the specific selection of genetic traits and in particular of sex. Further, the present invention finds applications in the development of contraceptiva.

Abstract: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter DNA which induces cell death, and a screening method for an apoptosis-suppressing agent using it.

Abstract: The present invention relates to an established cell line of microglia having the following properties: (a) form: having a macrophage-like or globular form in the presence of granulocyte-macrophage colony-stimulating factor. and in the absence of said factor, a branched form similar to branched microglia present in the brain, or both of the above forms; (b) functional characteristics: having specific affinity for the brain, and having a strong phagocytic ability; and (c) cell growth ability: growing depending on granulocyte-macrophage colony-stimulating factor. In particular, cell lines FERM BP-7061 and FERM BP-7062.

Abstract: The invention relates to the design, construction and use of eukaryotic cell lines useful in the identification of inhibitors of &bgr;-amyloid processing. More specifically, the invention relates to in vitro assays capable of identifying or quantifying a 4.2 kDa &bgr;-amyloid protein. The present invention also provides for DNA and protein molecules for the design, construction and use of eukaryotic cell lines useful in the identification of inhibitors of &bgr;-amyloid processing.

Abstract: The subject invention pertains to tumor cell lines useful for increasing the proliferation potential of any human or animal cell in culture, thereby providing immortalized or continuous cell lines and cultures. The invention also concerns proliferation factors, and compositions containing the factors, which are capable of increasing the proliferation potential of any human or other animal cell in culture. The subject invention further pertains to a method for proliferation cells in culture by contacting cells with the proliferation factors. The proliferated cells can range in plasticity and can include, for example, blast cells, fertilized ova, non-fertilized gametes, embryonic stem cells, adult stem cells, precursor or progenitor cells, and highly specialized cells. Optionally, the cells can be induced to cease proliferation.

Abstract: The invention relates to assays for screening growth factors, adhesion molecules, immunostimulatory molecules, extracellular matrix components and other materials, alone or in combination, simultaneously or temporally, for the ability to induce directed differentiation of pluripotent and multipotent stem cells.

Abstract: A cotton rat cell line, uses of cotton rat cells for growing, propagating, or culturing organisms, pathogens or viruses, such as PRRSV, and uses of the resultant organisms, pathogens or viruses, are disclosed.

Abstract: This invention provides a method for determining whether a compound is capable of suppressing ras functions comprising: (a) contacting an effective amount of the compound with Ha-ras transformed cloned rat embryo fibroblast cells under conditions permitting the compound to suppress ras functions in the cells; and (b) determining the expression or inhibition of certain indicator gene or genes, thereby determining whether the compound is capable of suppressing ras function. This invention further provides the determined compound and a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier. This invention also provides methods for generating transcriptional switched Ha-ras transformed cloned rat embryo fibroblast cells. This invention also provides the generated cells and different uses of the cells.

Abstract: The invention provides a method for freeze-drying spermatozoa to obtain at least one reconstituted spermatozoon whose head (nucleus) is capable of fertilizing an oocyte to produce a live offspring. The motility of spermatozoa which have been freeze-dried and stored in a vacuum at room temperature is not restored when rehydrated. Their plasma membranes are disrupted and they are all “dead” in the conventional sense. However, when they are injected microsurgically into oocytes, their nuclei transform into male pronuclei and participate in normal embryonic development.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the lipase peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the lipase peptides, and methods of identifying modulators of the lipase peptides.

Abstract: This invention provides novel hippocampus-associated proteins and DNA sequences coding therefor. In an investigation of hippocampus-associated proteins by differential screening of a rat hippocampus cDNA library, a cDNA species encoding a novel protein designated Hct-1 was isolated and shown to be a to cytochromes P450. The use of hybridization probes based on the rat Hct-1 sequence has led to the identification of homologues in other mammalian species.

Abstract: The present invention is directed to a novel receptor for galanin which has been designated as galanin receptor 2. The invention encompasses both the receptor protein as well as nucleic acids encoding the protein. In addition, the present invention is directed to methods and compositions which rely upon either GAL-R2 proteins or nucleic acids.

Abstract: To provide an immortalized capillary pericyte line which maintains the original function/property of the cell line-deriving tissue, its establishment method, and the screening method for useful substance using the immortalized capillary pericyte line. Cerebral tissue of a transgenic rat carrying the large T antigen gene of SV40 thermo-sensitive mutant line tsA58 is homogenized and the resultant brain capillaries are treated with protease, thus obtained brain capillary cells are subcultured to establish an immortalized cell that expresses SV40 thermo-sensitive large T antigen, PDGF receptor &bgr;, and Angiopoietin-1. In addition, the immortalized vascular pericyte line has ability to deposit calcium on matrix by dense culture.

Abstract: Human, swine and rat growth hormone secretagogue receptors have been isolated, cloned and sequenced. Growth hormone secretagogue receptors are new members of the G-protein family of receptors. The growth hormone secretagogue receptors may be used to screen and identify compounds which bind to the growth hormone secretagogue receptor. Such compounds may be used in the treatment of conditions which occur when there is a shortage of growth hormone, such as observed in growth hormone deficient children, elderly patients with musculoskeletal impairment and recovering from hip fracture and osteoporosis.

Abstract: Disclosed is a null mutant (or knockout) rodent comprising in its germ cells an artificially induced PTTG null mutation. In some embodiments, the null mutant rodent can be generated by way of homologous recombination in an embryonic stem cell or germ cell. The inventive null mutant rodent can be used to study mammalian physiology at the cellular, tissue, and/or organismal level with respect to various phenotypes, including hyperglycemia, hypoinsulinaemia, hypoleptinemia, diabetes, chromosomal aneuploidy, premature centromere division, chromosomal damage, aberrant mitotic cellular division, thrombocytopenia, thymic hyperplasia, splenic hypoplasia, testicular hypoplasia, and female subfertility. Also disclosed is an animal model for diabetes. Also disclosed is a somatic or germ cell obtained from the null mutant rodent. Also disclosed is a cell line derived from a cell obtained from the null mutant rodent.

Abstract: We previously described a novel in vitro model of a non-productive herpes simplex virus type 1 (HSV-1) infection in neurally-differentiated (ND)-PC12 cells that allows for inducible virus replication upon forskolin and heat stress (HS) treatment. In this research, we further characterized the model with respect to HSV-2 strain 333. We found that: (i) ND-PC12 cells are non-permissive to HSV-2 replication; (ii) HSV-2 can establish a quiescent infection, like HSV-1, in ND-PC12 cells with the transient use of acycloguanosine (ACV); however unlike HSV-1, anti-viral conditions are not obligatory to establish and maintain a quiescent state; (iii) the quiescent state is maintained in the presence of Vero cell cocultivation indicating that such cultures are free of infectious virus; and (iv) a high percentage of quiescently infected (QIF)-PC 12 cell cultures (80-100%) produce HSV-2 in response to forskolin and HS (43° C., 3 h) treatment for as long as 4 weeks post infection.

Abstract: The present invention provides mammalian cells and mammalian animals that produce HIV particles. The rodent animals of the present invention are able to stably express a human CD4, a human chemokine receptor (such as CXCR4 or CCR5), a human cyclin T1, and a human class II transactivator (CIITA), and produce HIV virus particles. Also provided are methods of preparing the transgenic cells and rodent animals of the invention, as well as methods of using them to identify and assay test agents for anti-HIV activity. Also provided are methods and pharmaceutical compositions for treating and preventing HIV infection in a mammal.

Abstract: The JeT promoter is a recombinant promoter with transcriptional activity comparable to a number of strong mammalian promoters. The promoter consists of five key elements: (1) a TATA box; (2) a transcription initiation site (Inr); (3) a CAT consensus sequence in conjunction with (4) a CArG element and finally, (5) four Sp1 transcription binding sites (GGGCGG) arranged in two tandems.

Abstract: The present invention relates to isolated and/or purified rat apoptosis-specific eucaryotic initiation Factor-5A (eIF-5A) and deoxyhypusine synthase (DHS) nucleic acids and polypeptides. The present invention also relates to methods of modulating apoptosis using apoptosis-specific eIF-5A and DHS, and antisense oligonucleotides and expression vectors of apoptosis-specific eIF-5A and DHS useful in such methods.

Abstract: The present invention relates to a method of isolating ependymal neural CNS stem cells from a post-natal animal or a human, which method comprises the steps of (a) screening single cells obtained by dissociating CNS tissue from said animal for cells exhibiting at least one characteristic of an ependymal neural stem cell; and (b) recovering the cells that exhibit the characteristic or characteristics screened for in step (a). The screening may be performed for a specific cell surface protein or by previously labeling the ependymal cells. The invention also relates to isolated ependymal neural CNS stem cells, in vitro and in vivo assays based on the findings according to the invention and various uses of the ependymal neural stem cells according to the invention.

Abstract: The present invention embodies a method of transducing marrow stromal cells with retroviral vectors comprising the TH and GC enzyme precursors of L-DOPA. The invention also describes a method of producing exogenous L-DOPA using this transduction method. Novel retroviral vectors comprising TH and GC, with an intervening IRES are also described.

Abstract: The present invention relates to isolated and/or purified rat apoptosis-specific eucaryotic initiation Factor-5A (eIF-5A) and deoxyhypusine synthase (DHS) nucleic acids and polypeptides. The present invention also relates to methods of modulating apoptosis using apoptosis-specific eIF-5A and DHS, and antisense oligonucleotides and expression vectors of apoptosis-specific eIF-5A and DHS useful in such methods.