Abstract: A recombinant nucleic acid construct is presented in which a mouse uroplakin-II (UP-II) gene promoter is coupled to a heterologous gene of interest. When the resultant construct is introduced into a transgenic mouse, the UP-II promoter directs the expression of the heterologous gene in the urothelium of the said mouse.

Abstract: The present invention concerns a method and compositions of matter useful for the method of making, in transgenic animals, a human hemoglobin that is more stable and more readily purified from the endogenous hemoglobins of the transgenic animal than hemoglobin A. The hemoglobins produced by the invention include hemoglobin A.sub.2, which is an .beta..sub.2 .delta..sub.2 tetramer, as well as other hemoglobins having similar properties to hemoglobin A.sub.2 and have .beta./.delta.chimeric globins. The specification discloses a chimeric gene, encoding a human .delta.-globin that is expressed in transgenic animals at levels approximating the level of expression of the .alpha. or .beta. globin.

Abstract: Method for in vivo introduction of a nucleic acid cassette into stem cells of intestinal epithelium. The nucleic acid cassette is introduced via vector solution. The vector solution can be delivered via the intestinal lumen in a variety of ways, including through an insertion device such as an endoscope, through catheters, through ligating and clamping the intestine after laparotomy or through slow release capsules. The vector solution once introduced into the intestinal epithelium is allowed to contact the stem cells for sufficient time for incorporation, usually between 1 and 48 hours. After sufficient incorporation, the insertion device and/or clamping and ligation procedure blockage are removed. Preferably, the procedure includes sufficient fluid to distend the intestine and provide additional access to the stem cells and the crypts.

Abstract: Gene-targeted heterozygous and homozygous SOD-1 null non-human mammals, methods for producing them, and methods for use are described. Deletion vectors and gene-targeted cells are also described, as are methods for producing and using the same.

Abstract: The invention relates to the human herpesvirus type 6 protein p100 and parts thereof having its specific immunological properties. It further relates to antibodies directed to them and to the corresponding DNA sequences. They can be used in pharmaceutical or diagnostic compositions, optionally together with other HHV-6 proteins or the corresponding DNA sequences.

Abstract: The present invention provides a nucleic acid molecule encoding a mammalian retinoblastoma protein-interacting zinc finger (RIZ) protein, which binds retinoblastoma protein. In addition, the invention provides methods for reducing the growth of a tumor cell by introducing a nucleic acid molecule encoding a RIZ into the tumor cell.

Abstract: A method of preparing xenogeneic anti-hepatitis virus antibodies from a chimeric mouse or rat host is taught. In this method, tissues including liver tissue of mammals that can be infected with hepatitis virus are transplanted into a mouse or rat and immune cells are subsequently recovered from the transplanted animal. These immune cells are then selected for cells or antibodies that have anti-hepatitis virus reactivity.

Abstract: A composition containing a recombinant plasmid which includes an exogenous nucleotide sequence capable of expressing a compound including an amino acid sequence in a host organism. The composition includes an emulsion comprising at least one aqueous phase and at least one oily phase, the recombinant plasmid being contained in at least one of phases. A vaccine and a curative drug including the composition are also disclosed.

Abstract: The invention includes an artificial PrP gene, a transgenic animal containing a PrP gene of another animal or the artificial PrP gene, a hybrid non-human mammal with an ablated endogenous prion protein gene and exogenous prion protein gene, assay methodology which uses the animals to detect pathogenic prions in a sample and standardized prion preparation used in the assay. The genome of a host animal (such as a mouse), is manipulated so that the animal is rendered susceptible to infection with prions which normally would infect only a genetically diverse test animal (such as human, cow or sheep). A PrP gene of the host is preferably manipulated to include a mutation which matches a mutation which causes prion disease in the genetically diverse mammal. Pathogenic prions in a sample can be detected by injecting the sample to be tested into a mammal of the invention which has been genetically manipulated so as to be susceptible to infection from prions in the sample.

Abstract: The invention concerns populations of homogenous, post-mitotic human NT2N neurons that are useful for generating animal systems for study of neuron function. Also disclosed are methods of preparing animals that are useful for study of neurological function. In these methods, differentiated NT2N cells are stably implanted into host rodent animals.

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.

Abstract: 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.

Abstract: A knockout mouse containing a non-functional allele for the gene that naturally encodes and expresses functional DARPP-32 is disclosed. This mouse contains two non-functional alleles for the gene that naturally encodes and expresses functional DARPP-32, and therefore is unable to express functional DARPP-32. This mouse finds utility as a screening model for potential therapeutic agents useful in the treatment of schizophrenia, Parkinson's disease, and the treatment of addictions, especially those involving drugs of abuse.

Abstract: A method for genetically engineering cells to produce soluble and secretable Golgi processing enzymes instead of naturally occurring membrane-bound enzymes. Cells are genetically engineered to express glycosyltransferases which lack both a membrane anchor and a retention signal. The resulting altered enzyme becomes soluble and secretable by the cell without losing its catalytic activity. Secretion of the soluble glycosyltransferase by the cell provides for increased production and simplified recovery of glycosyltransferase.

Abstract: The invention provides transgenic non-human animals in which genes encoding colony-stimulating factors have been specifically disrupted, so that the animals do not express the respective factors. In specific embodiments the invention provides mice in which expression of GM-CSF, G-CSF and/or CSF-1 is disrupted. These animals do not produce any bioactive CSF of the respective type. They are useful as models for a variety of conditions, and particularly for testing of therapeutic methods.

Abstract: The present invention relates to methods of therapeutic or prophylactic treatment of connective tissue diseases by systemic or local delivery of a nucleic acid sequence to a mammalian host. Expression of the nucleic acid sequence results in the systemic delivery of a biologically active protein or peptide which acts to antagonize inflammatory, hypertrophic and erosive phenomenon associated with connective tissue disease. Systemic delivery of such gene products results in sustained treatment of connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus.

Abstract: A process is described for the screening of an agent to determine its effect on the frequency of genome rearrangement in mammals. In particular, mice harboring a p.sup.un mutation are exposed to an agent of interest and the frequency of genome rearrangement relative to that observed in an unexposed mouse is determined. The relative frequency of rearrangement represents a measure of the effect of the agent on the host animal.

Abstract: The invention includes an artificial PrP gene, a transgenic animal containing a PrP gene of another animal or the artificial PrP gene, a hybrid non-human mammal with an ablated endogenous prion gene and exogenous prion gene and assay methodology which uses the animals to detect pathogenic prions in a sample or diagnose a cause of death. The artificial gene includes a sequence such that when it is inserted into the genome of a host animal (such as a mouse), the animal is rendered susceptible to infection with prions which normally would infect only a genetically diverse test animal (such as human, cow or sheep). The artificial PrP gene may be comprised of a completely artificial polynucleotide sequence. Alternatively, the artificial gene may be comprised of the codon sequence of a host animal with one or more codon substitutions being made wherein the substitutions are preferably corresponding PrP gene codons from a genetically diverse test animal.

Abstract: The invention relates to compositions of erythrocytes that have been modified following hypotonic lysis and resealing by addition of 2',3'-dideoxycytidine-5'-triphosphate (ddCTP) or 3'-azido-3'-deoxythymidine-5'-triphosphate (AZT-TP). These compositions may also contain ATP. Also disclosed are methods of preparing these compositions.

Abstract: Methods of treating diseases or conditions, characterized by elevated serum lipoprotein levels, by providing elevated levels of a VLDL receptor in an animal, e.g., a human are set forth. Such receptors aid in removal of circulating VLDL and related lipoproteins, and thus decrease the risk of developing coronary diseases or conditions or decrease the severity of such diseases or conditions. Clones of human and mouse VLDL receptor which can be used in the invention are also provided. Vectors for the expression of VLDL receptors, stably transfected and transformed cells and transgenic animals are also provided.