Abstract: Disclosed a transgenic non-human mammal whose germ cells and somatic cells contain a knockout mutation in DNA encoding .beta..sub.3 -adrenergic receptor polypeptide.

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 present invention relates to novel recombinant AAV (Adeno-associated virus) vectors that may be used to direct integration of recombinant DNA sequences into specific regions of the human host genome. These vectors may be used in gene therapies designed to replace or supplement defective genetic information with normal genetic information. The invention also relates to the isolation and characterization of the specific cellular host sequences, herein referred to as host target sequences, that signal the integration of AAV recombinant DNA sequences into specific regions of the host genome. Transgenic animals containing the generated target sequences may be as used as model is systems for testing of AAV based gene therapies.

Abstract: The present invention provides a novel family of apoptosis-modulating proteins. Nucleotide and amino acid residue sequences and methods of use thereof are also provided.

Abstract: A transgenic mouse that expresses the human Apo E isoforms Apo E2, Apo E3 or Apo E4 but is essentially incapable of expressing endogenous Apo E. Additionally, mice that express more than one of these isoforms are produced by selectively breeding the transgenic mice expressing the different Apo E isoforms disclosed herein. Thus, the present invention allows, among other things, the study of the effects of different combinations of human Apo E isoform expression on normal brain biology, development, function, aging and injury.

Abstract: Immortalized cell lines derived from normal adult human liver are described which express phenotypic characteristics of normal adult liver epithelial cells. The invention further provides methods of using the immortalized cells to evaluate the cytotoxicity or carcinogenicity of a compound.

Abstract: There is provided a mouse lacking the function of the endotheline-1 gene by insertion of another gene into the endotheline-1 gene.The mouse is useful for elucidation of the pathological physiology and causes of and development of therapies for cardiovascular diseases such as hypertension, arteriosclerosis and ischemic heart disease.

Abstract: The presence of clonal macrophages in pre-cancerous and cancerous tissue represents an early stage of the disease in which clonal expansion of macrophages occurs due to HIV integration or other genetic mutation. Clonally expanded macrophages induce proliferation of surrounding tissue leading to cancerous tumor growth. The invention provides methods and kits for diagnosis of HIV- and non-HIV-associated clonal expansion of macrophages in pre-cancerous and cancerous tissue. The invention also provides methods for the treatment of cancers induced by clonal macrophage expansion and proliferation of surrounding tissue.

Abstract: The invention provides retroviral vectors which can be used for directing gene delivery to a specific sub-population of mammalian cells. The vectors comprise chimeric targeting proteins which specifically alter the host range of the vector. The chimeric targeting proteins contain a ligand moiety which is capable of binding to receptors present on target cells, and an uptake moiety which is capable of promoting entry of the vector into the target cell. The ligand moiety is derived from a cytokine that acts upon the target cells of interest, and the uptake moiety is derived from a retroviral envelope protein.

Abstract: Methods for treating respiratory disease, including cystic fibrosis, emphysema, bronchitis, and sinusitis are presented. Methods comprise administering to a patient an effective amount of DNA in a manner so as not to effect gene transfer and expression.

Abstract: The present invention provides a mammalian artificial chromosome (MAC), comprising a centromere and a unique cloning site, said MAC containing less than 0.1% of the DNA present in a normal haploid genome of the mammalian cell from which the centromere was obtained. The invention further provides a MAC, wherein the unique cloning site is a nucleic acid sequence encoding a selectable marker. The invention also provides methods of preparing a MAC. In addition, the invention provides methods of stably expressing a selectable marker in a cell, comprising introducing a MAC containing the selectable marker into the cell. The invention also provides a cell containing a MAC expressing an exogenous nucleic acid sequence and a transgenic mammal expressing a selectable marker.

Abstract: Disclosed is a mouse in which expression of the gene encoding the CTLA-4 receptor is suppressed. Also disclosed is a nucleic acid construct useful in preparing such a mouse, and a cell line containing such construct.

Abstract: Vectors, or naked DNA, containing a promoter for an FSP1 gene and a downstream gene capable of attenuating fibroblasts and their function are provided. Methods of using these vectors to inhibit tissue injury related to fibrogenesis are also provided.