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 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: Transgenic mice carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline operatively linked to a second polypeptide activates transcription in eukaryotic cells. In a preferred embodiment, the transgene encoding the transcriptional activator fusion protein is integrated at a predetermined location within the chromosome of the transgenic mouse.

Abstract: A simple, rapid method for creating a lipidic vector for delivery of a therapeutic molecule entails bringing the molecule into contact with a polycation, thereby forming a complex, and then mixing the complex with an anionic lipidic preparation. Tissue-specific targeting peptides, fusogenic peptides and nucleus-targeting peptides also can be added to the lipid preparation. The result is a stable lipidic vector of reduced immunogenicity and cytotoxicity. The vector also displays enhanced transfection activity.

Abstract: A suspension comprising human neutrophil precursor cells, wherein the cellular component is comprised of at least about 16% human myeloblasts and promyeclocytes, which have been derived from neutrophis progenitor cells obtained from peripheral blood, bone marrow or cord blood, and less than about 5% colony forming units (CFU) of at least about 50 cells is provided. An alternative suspension comprising human neutrophil precursor cells, wherein the cellular component is comprised of at least about 16% CD15+CD11b- cells and less than about 5% colony forming units (CFU) of at least about 50 cells also is provided, wherein at least about 60% of the CD15+CD11b- cells are myeloblasts and promyelocytes. The suspensions of the invention are useful in methods for increasing neutrophil populations in a patient having a reduced populations of neutrophils.

Abstract: A method for introducing and expressing genes in animal cells is disclosed comprising infecting said animal cells with live invasive bacteria, wherein said bacteria contain a eukaryotic expression cassette encoding said gene. The gene may encode, e.g., a vaccine antigen, an therapeutic agent, an immunoregulatory agent or a anti-sense RNA or a catalytic RNA.

Abstract: A method of gene transfer involving administering a recombinant adeno-associated virus (AAV) bearing the desired gene into the muscle of the animal is described.

Abstract: The present invention concerns defective recombinant adenoviruses containing an inserted gene encoding apolipoproteins, pharmaceutical compositions comprising the adenovirus, and their use for the treatment or prevention of pathologies linked to dyslipoproteinemias.

Abstract: Transgenic mice carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates transcription of a tet operator-linked gene in eucaryotic cells, and the second comprising a gene operably linked to a minimal promotor operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic mice having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to a mouse of the invention are also disclosed.

Abstract: In vivo and in vitro methods of increasing amyloid deposition using amyloid-enhancing compounds are described. Methods of forming amyloid fibrils and screening for agents useful in treating amyloidosis are also described. Animals having non-naturally occurring amyloid deposits produced using the amyloid-enhancing compounds even further are described.

Abstract: HIV-1 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 or ameliorating disease caused by this virus. The instant invention provides an animal model for HIV-1 induced disease, virus for generating such model animals, and methods for generating pathogenic SHIV.

Abstract: Transgenic mice carrying a recombinant DNA construct comprising the gene encoding diphtheria toxin A chain operably linked to a osteocalcin promoter. The transgenic mice can be used as a model for metabolic bone diseases since they have decreased bone mass associated with a marked reduction in the number of osteoblasts.

Abstract: The present invention relates to a transgenic mouse deficient in T-cells, which is provided by fusing human heat shock protein (Hsp) gene with H2K promoter and transferring it to a mouse. Transgenic mouse line with a shrunken thymus and edficient in T-cells not having mature T-cells can be obtained.

Abstract: A transgenic mouse containing an IGF-1 transgene which is operably linked to a promoter sequence and is expressed in the pancreas of the mouse.

Abstract: Invertebrate and vertebrate patched genes are provided, including the mouse and human patched genes, as well as methods for isolation of related genes, where the genes may be of different species or in the same family. Having the ability to regulate the expression of the patched gene, allows for the elucidation of embryonic development, cellular regulation associated with signal transduction by the patched gene, the identification of agonist and antagonist to signal transduction, identification of ligands for binding to patched, isolation of the ligands, and assaying for levels of transcription and expression of the patched gene.

Abstract: The present invention provides a method for inducing reendothelialization of the lining of an injured blood vessel comprising contacting the injured portion of the vessel with nucleic acid encoding an endothelial cell mitogen such as vascular endothelial growth factor (VEGF) operably linked to a promoter to result in expression of the mitogen when delivered to the cells at the site of vascular injury. The resulting reendothelialization of the injured blood vessel inhibits smooth muscle cell proliferation and consequently reduces restenosis. The methods of the present invention may be used to treat any blood vessel injury that results in denuding of the endothelial lining of the vessel wall, including, for example, those injuries resulting from balloon angioplasty and deployment of endovascular stents.

Abstract: Disclosed in this invention is a transgenic mouse containing rcombinant DNA including a promoter and a heat shock protein 70 gene attached to downstream of the promoter. Transgenic mice line inducing non-insulin dependent diabetes having a blood glucose level of 300 mg/dl was obtained.

Abstract: Recombinant transgenic mice expressing leukemia inhibitory factor (LIF) in the pituitary. The transgenic mice of the invention are suitable for use as animal models of pituitary disorders, as well as for identifying compounds which stimulate growth hormone production, for the treatment of physiological disorders associated with growth retardation and pituitary developmental retardation disorders, such as chraneopharyngioma, and pituitary cysts, among others.

Abstract: The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.