Abstract: The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. In another embodiment, the expression of the endogenous gene may be further increased by co-integration of one or more amplifiable markers, and selecting for increased copies of the one or more amplifiable markers located on the integrated vector. In another embodiment, the invention is directed to activation of endogenous genes by non-targeted integration of specialized activation vectors, which are provided by the invention, into the genome of a host cell.

Abstract: The present invention relates to human bile salt-stimulated lipase (BSSL) obtainable from transgenic sheep. The invention further relates to transgenic sheep whose germ cells and somatic cells contain a recombinant nucleotide molecule comprising a nucleotide sequence encoding for human BSSL. The invention also relates to methods for producing said transgenic animals, as well as to methods for producing human BSSL derived from transgenic animals. In addition, the invention provides the use of compositions comprising BSSL in the treatment of diseases relating to exocrine pancreatic insufficiency, and for improvement of the utilization of dietary lipids in preterm born infants.

Abstract: Expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. The invention also provides methods for the isolation of nucleic acid molecules (particularly cDNA molecules) encoding a variety of proteins, including transmembrane proteins, and for the isolation of cells expressing such transmembrane proteins which may be heterologous transmembrane proteins. Thus, by the present invention, endogenous genes, including those associated with human disease and development, may be activated and isolated without prior knowledge of the sequence, structure, function, or expression profile of the genes.

Abstract: Disclosed are methods and compositions comprising a novel osteoblast-specific transcription factor designated Osf2/Cbfa1. Also disclosed are nucleic acid segments encoding this polypeptide derived from human cell lines, and the use of these polynucleotides in a variety of diagnostic and therapeutic applications. Methods, compositions, kits, and devices are also provided for identifying compounds which are inhibitors of osteoblast differentiation, and identifying Osf2/Cbfa1 polynucleotides and polypeptides in a sample. Also disclosed are nucleic acid compositions comprising an Osf2 promoter, and the use of the promoter in heterologous and homologous gene transcription and protein production.

Abstract: Tandem pore domain weak inward rectifying K+ (TWIK) channel nucleic acids and proteins that have been isolated from Drosophila melanogaster and Leptinotarsa are described. The TWIK channel nucleic acids and proteins can be used to genetically modify metazoan invertebrate organisms, such as insects, coelomates, and pseudocoelomates, or cultured cells, resulting in TWIK channel expression or mis-expression. The genetically modified organisms or cells can be used in screening assays to identify candidate compounds which are potential pesticidal agents or therapeutics that interact with TWIK channel proteins. They can also be used in methods for studying TWIK channel activity and identifying other genes that modulate the function of, or interact with, the TWIK channel gene.

Abstract: The invention concerns an improvement in the art of inserting and expressing foreign gene into eukaryotic cells. The invention particularly concerns methods and compositions whereby viral vectors can be used to insert and express foreign genes into specifically cells having particular differentiation antigens. A method of determining which differentiation antigens can be used is taught. The invention encompasses complexes of viral particles and adapters that cause the binding and internalization of the vector particles such that a gene of interest in the particle is expressed.

Abstract: A method to prevent graft rejection of transplanted cells, tissues or organs without general immunosuppression is described. The method employs a newly discovered protein, LAG-3. When allogeneic or xenogeneic cells are engineered to express LAG-3 on their surface and transplanted, immune destruction of the implanted cell, tissue or organ is prevented, while the host's immune system remains functional. A particular application of this method allows the preparation of a universal gene therapy host cell expressing LAG-3 on its surface for protection from graft rejection by a host's immune system.

Abstract: Methods are provided for altering levels of syndecan within a cell. The methods include enhancing syndecan expression via administration of growth factors, preventing suppression of syndecan expression via administration of anti-steroid agents, and altering syndecan biochemistry within the cell. The methods are used to induce or maintain cellular differentiation, and to decrease the growth of malignant cells. Application of the methods to the treatment of patients, including humans, is provided. A syndecan enhancer element, novel proteins that activate the enhancer element, non-human transgenic animals comprising this enhancer element linked to a structural gene, and the use of this enhancer element to regulate the expression of syndecan and other genes are also provided. The enhancer element can also be used to target expression of a gene to wound sites.

Abstract: The present invention provides transgenic fish whose somatic and germ cells contain a genomically integrated plasmid containing a heterologous mutation target nucleic acid sequence that is detectable via bioassay in a bacterial cell into which the target nucleic acid has been introduced. The frequency and character of mutations in the mutatable target nucleic acid sequence following exposure of the transgenic fish to one or more potentially mutagenic agents can thus be evaluated.

Abstract: The invention provides a swine which is homozygous for a major histocompatibility complex haplotype and at least 60% homozygous at all other genetic loci and such animal is propagatable, and a cell or an organ derived therefrom. The invention also provides a method for providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, as well as a method of inducing tolerance in a recipient mammal of a first species to a graft from a donor mammal of a second species.

Abstract: Disclosed are isolated transposable elements, or isolated DNA sequences which encode a transposase protein (or a portion of a transposase protein), The isolated transposable elements or the isolated DNA sequences being characterized by the ability to hybridize to the DNA sequence of Minos 1 under stringent hybridization conditions. The invention also relates to a purified transposase protein, or peptide fragments thereof, encoded by such DNA sequences. Such transposable are useful in methods for the stable introduction of a DNA sequence of interest into a eukaryotic cell. The sequence information disclosed herein is useful in the design of oligonucleotide primers which are useful for the isolation of related members of the Tc-1 family of transposable elements.

Abstract: Transgenic non-human animals one having a general deletor construct and a second having a general reporter construct are described. The general deletor animals express a heterologous recombinase under the control of an ubiquitously expressed endogenous promoter. Specifically, the Cre recombinase is inserted into the ROSA26 locus of the mouse. The general reporter animals have a gene which is desired to remove flanked by sites recognized by the is heterologous recombinase. This flanked sequence is operatively associated with a marker gene such that when the gene sequence flanked by sites recognized by the heterologous recombinase is excised, the reporter gene is expressed. When the general deletor mouse is crossed with the general reporter mouse the heterologous recombinase is expressed in essentially all cells of the resultant descendants under the control of the ubiquitous promoter. Expression of the recombinase results in the excision of the desired gene in essentially all cells of the descendant animals.

Abstract: The present invention provides improved methods for detection of recombinant proteins. The fusion proteins of the invention comprise a capture tag sequence, a detection tag sequence, and polypeptide sequence of interest.

Abstract: The invention relates to a putative human tumor suppressor protein identified as a novel GAP protein, designated “E6TP1” (for E6-targeted protein), its nucleic acid and amino acid sequences, and methods of use thereof in the regulation of small G protein signaling pathways. In addition, methods of use of E6TP1 as a Therapeutic for treatment or prevention of carcinomas, especially HPV-associated carcinomas of anogenital origin, and other diseases is encompassed in the invention.

Abstract: The present invention provides methods for administering an adenoviral gene transfer vector comprising an exogenous gene to an animal. One method involves utilizing systemic neutralizing antibodies to neutralize the adenoviral gene transfer vector outside a targeted muscle. Another method involves the repeat administration of an adenoviral gene transfer vector to a skeletal muscle.

Abstract: The invention provides ratC polypeptides and polynucleotides encoding ratC polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing ratC polypeptides to screen for antibacterial compounds.

Abstract: The invention provides an endometriosis mouse model wherein severely compromised immune deficient (SCID) female mice are transplanted with human xenografts of normal endometrial tissue, but result in mice with human endometriosis. Typically, the xenografts are treated with a micronized estrogen source prior to transplantation or implantation and the endogenous progesterone of the mice is eliminated also prior to transplantation of the human xenograft. These diseased mice are useful in the study of endometriosis.

Abstract: Vectors which establish controlled expression of recombinant GHRH genes within tissues at certain levels. The vector includes a 5′ flanking region which includes necessary sequences for expression of a nucleic acid cassette, a 3′ flanking region including a 3′UTR and/or 3′NCR, and a linker which connects the 5′ flanking region to a nucleic acid sequence. The linker has a position for inserting a nucleic acid cassette. The linker does not contain the coding sequence of a gene that the linker is naturally associated with. The 3′ flanking region is 3′ to the position for inserting the nucleic acid cassette.

Abstract: The present invention relates to a novel gene, Di12, that is differentially expressed as a 1.35 kb RNA in breast cancer tissues and cell lines, and in several normal tissues. The full length cDNA encodes a protein of 339 amino acids. Antibodies to the gene product were developed to investigate the expression of Di12 in breast cancer cell-lines and tumors. The Di12 protein was found in tissue sections of infiltrating ductal carcinomas (IDCs), but not in benign or normal breast specimens. Di12 wag also present in IDC-breast cancer patient sera, and its expression level increased markedly if IDC was accompanied by lymph node or distal metastases. As IDC constitutes ˜70% of breast cancers seen clinically, the level of Di12 expression is useful for diseases diagnosis predicting disease progression and monitoring a therapeutic treatment.

Abstract: Novel human Kv4.3 polypeptides, polynucleotides which encode these polypeptides, and methods for producing these polypeptides are provided. Diagnostic, therapeutic, and screening methods employing the polynucleotides and polypeptides of the present invention are also provided.