Abstract: This disclosure relates to a method of specifically decorating selected mammalian chromosomes and of detecting, identifying and and/or quantitating selected individual chromosomes, by means of chromosomal in situ suppression (CISS) hybridization. The method is useful in analyzing cells for the occurrence of chromosomes, chromosome fragments or chromosome aberrations.

Abstract: The generation of transgenic animal models for testing various treatments of Type II Diabetes Mellitus are described. The DNA construct allows pancreatic &bgr; cell-specific expression of human islet associated polypeptide (IAPP) under the regulation of the rat insulin II promoter in both cell lines and transgenic animals. The DNA construct is introduced into animal embryos by microinjection as one or multiple copies or into established cell lines by electroporation. The transgenic animals develop amyloid plaque deposits in the islets of Langerhans in the pancreas, fasting hyperglycemia, glycouria and diabetic glomerulosclerosis at 3 to 5 months of age. The cell lines can be screened for treatments that inhibit expression of human IAPP; the transgenic animals can be screened for treatments that either enhance or inhibit the progression of this disease phenotype.

Abstract: The present invention relates to methods of treatment of programmed cell death (apoptosis) through the use of the HSV-1 gene &ggr;134.5 or the product of its expression, ICP34.5. The gene and its expression have been demonstrated to be.required for HSV-1 neurovirulence, and in particular, to act as an inhibitor of neuronal programmed cell death which allows for viral replication. Use of the gene therapy, or the protein itself, can be expected to result in inhibition of programmed cell death in various neurodegenerative diseases. This invention also relates to novel vectors for gene therapy, including modified herpes virus. Methods are presented for conducting assays for substances capable of mimicing, potentiating or inhibiting the expression of &ggr;134.5 or the activity of ICP34.5. Also, methods are disclosed for the treatment of tumorogenic diseases, including cancer, and for treatment of herpes and other viral infections using inhibitors of &ggr;134.5 expression or ICP34.5 activity.

Abstract: 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.

Abstract: The chimeric gene is directed by a promoter or fusion of promoters which preferably are regulable and activated by the diabetic process. Preferably, it is obtained by fusion of the human insulin gene to the promoter of PEPCK (P-enolpiruvate carboxiquinasa). Said promoter (fragment -460 bp to +73 bp) is fused to the flank zone 5' of the human insulin gene (-170 bp to +1). The gene of the human insulin contains two coding exons E1 and E2 and two introns A and B. It also relates to an expression vector which allows the expression of insulin in cells which are different from the .beta.-cells of the pancreas, and to a transgenic mouse which expresses said chimeric gene.

Abstract: The present invention relates to a replication deficient recombinant adenovirus vector in the genome of which is inserted an expression cassette comprising the DNA fragment coding for the human CFTR protein, said DNA fragment being placed under the control of the elements for the expression thereof.The present invention also concerns a vector according to claim 1 wherein in the expression cassette the human CFTR gene is under the control of the endogenous human CFTR promoter.

Abstract: The invention claims a class of adenovirus vectors for delivering recombinases to a large number of cells of different origins, and methods for regulating the expression of a gene in transfected mammalian cells in culture and in cells of transgenic animals, comprising infecting said cells with an Ad vector encoding a recombinase whose target site is present at or adjacent to the gene, wherein the action of the recombinase regulates the expression of said gene.

Abstract: Disclosed are methods for use in transferring nucleic acids into central nervous system cells in vivo and in vitro and/or for stimulating central nervous system cells. Neurotrophic genes are shown to stimulate neurofilament cells and to promote nerve cell growth, repair and regeneration in vivo. Gene transfer protocols are disclosed for use in transferring various nucleic acid materials into central nervous system cells, as may be used in treating various pathologies of the brain and spinal cord.

Abstract: The invention relates to DNA constructs comprising an exogenous DNA sequence encoding a therapeutic protein product or itself a therapeutic product, DNA sequences derived from SV40 for replication and packaging of said construct into pseudovirions, and a DNA sequence encoding one or more regulatory elements sufficient for the expression of said therapeutic protein in a mammalian cell operatively linked thereto. The therapeutic product integrated into the DNA constructs of the invention can be a protein selected from the group consisting of enzymes, receptors, structural proteins, regulatory proteins and hormones. Of particular interest are .beta.-globin, P-glycoprotein and apolipoprotein A-I. Specific DNA constructs are plasmids pSO6.beta.-9, pSO6.beta.-1, pSO41, pSM1, and pSAIc. The invention also relates to SV40 pseudovirions containing a DNA construct according to the invention, which are capable of infecting and being expressed in mammalian cells.

Abstract: Transgenic mice with a non-functional proteinase activated receptor-2 (PAR2) gene are prepared by targeted disruption of the endogenous PAR2 gene. The resulting transgenic mice display a phenotype including a lack of a hypotensive response to administration of the peptide, SLIGRL, and a reduction in carrageenin-induced paw edema compared to wild type mice.

Abstract: The present invention provides a vector system that is useful for the generation of mutations in a recombination-based construction method. The invention further includes the incorporation of mutations generated by the method of the present invention into mouse embryonic stem cells and transgenic mice.

Abstract: The invention relates to endothelin-converting enzymes containing the polypeptide sequence described in SEQ. ID. NO. 30 or SEQ. ID. NO. 36 or functional fragments thereof, genes which code for such enzymes, and processes for producing the said enzymes and the use thereof.

Abstract: The present invention relates to compositions and methods for the screening of compounds for anticoagulant activity. In particular, the present invention relates to non-human transgenic animals expressing activated protein C ("APC")-resistant factor V proteins which display a predisposition toward spontaneous thrombosis. The present invention also provides methods for using these transgenic animals to screen compounds for anticoagulant activity.

Abstract: The present invention discloses MmRad51-deficient transgenic mice and mouse cells, as well as MmRad51/p53-deficient transgenic mice and mouse cells. Also described is a method of screening for proteins that rescue the senescence phenotype in MmRad51/p53-deficient cells.

Abstract: It is known that the human influenza virus strain A/Puerto Rico/8/34 grows particularly well in eggs and that reasserted viruses having it as a parent may also grow well in eggs. It has now been found that certain reassortants of A/PR/8/34 and equine influenza viruses, namely those which comprise the RNA7 segment from A/PR/8/34, will grow in cell culture, even though the parent equine influenza virus will not.Thus the specification describes and claims: reassorted viruses comprising genes for surface antigens of equine influenza viruses and the RNA7 segment from A/PR/8/34; methods of obtaining such viruses by reassortment; methods of propagating such reasserted viruses in cell culture, especially Vero cells; vaccines against equine influenza comprising such reassorted viruses; and methods of vaccinating equines against influenza.

Abstract: A hairless mouse designated NS:Hr/ICR is sensitive to H. pylori. This NS:Hr/ICR hairless mouse can be easily infected with H. pylori in its alimentary canal, and is therefore useful as an experimental animal model for H. pylori infection.

Abstract: 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.

Abstract: A transgenic mouse is provided, the cells of which contain and express IL-5 in a cell type- or tissue-specific manner and in an amount which results in an IL-5-associated pathology. Also provided are expression cassettes comprising an IL-5 gene, operably linked to a cell type- or tissue-specific transcriptional control sequence and methods of using transgenic mice comprising the expression cassettes.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are calls which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: A murine model for human ovarian and prostate cancer is provided. The model comprises an immunodeficient mouse containing human primary ovarian or prostate carcinoma tissue implanted within the gonadal fat pad. Methods of using the murine model, for example, to grow tumors and to screen treatments for ovarian and/or prostate cancer are also provided.