Abstract: The present invention concerns products and methods particularly useful for activating and analyzing non-dividing cell nuclei. The featured products include activating egg extracts, cytostatic factor (CSF) extracts, kits containing these extracts, and a microchamber microscope slide useful in analyzing nucleus activation.

Abstract: A method is provided for repopulating degenerated of immunetolerant mice which lack mature B and T lymphocytes with xenogenic mammalian hepatocytes, particularly primate hepatocytes to generate chimeric mice. In addition, a method of generating a human hepatitis virus-infected chimeric mouse is provided. A preferred xenogenic primate hepatocyte is derived from human, chimpanzee or baboon. These chimeric mice are useful in the investigation of host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis. Methods for monitoring the development of hepatitis and hepatocellular carcinoma as well as methods for testing and screening anti-viral and anti-cancer compounds with this model system are also provided.

Abstract: Disclosed is a TGC method for inducting targeted somatic transgenesis in an animal host, whereby bacteria with a foreign DNA integrated into an episomal vector release, under the control of eukaryotic regulatory elements for ulterior transcription and expression, said foreign DNA in the case of infection of a foreign organism, organ, tissue, cell line or individual cells, causing transcription and expression of foreign DNA and/or foreign protein in said location.

Abstract: Methods are provided for restoring wild-type p53 gene function to a cell. Such methods include gene therapy. Typically, this will stop tumor cells from proliferating.

Abstract: Disclosed is the sequence of the human ABC1 promoter, a method for expressing foreign DNA in host cells using the human ABC1 promoter, including a method of determining whether a chemical not previously known to be a modulator of the human ABC1 gene transcriptionally modulates the expression of the human ABC1 gene. Also disclosed is a sterol-responsive region of the human ABC1 promoter, along with a showing that it is activated by hydroxysterols and 9-cis-retinoic acid, implicating a mechanism of activation involving LXR/RXR heterodimers.

Abstract: Compositions and methods for using mammalian CCR8 receptor proteins, antagonists and related reagents to treat diseases or conditions associated with Th2-mediated responses in an individual, especially asthma, are provided. The methods comprise administering a therapeutically effective amount of a CCR8 antagonist, alone or in combination with other therapeutic reagents. Also provided are methods for screening for therapeutics. Genetically-engineered animals and their use as models of molecular mechanism are also provided.

Abstract: The present invention provides transgenic non-human animal models of basal cell carcinoma which allows for the characterization of the disease as well as for providing a system for the development and testing of potential treatments.

Abstract: The present invention relates to the synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitivity sites of the &bgr;-globin locus are sufficient to result in high level expression of human &agr;- or &bgr;-globin transgenes.

Abstract: The invention provides a microinsertion-based, trans-complementation method of in vitro oocyte activation useful to identify properties of sperm-borne oocyte-activating factor(s) (SOAF) and ooplasmic interactions with sperm components at fertilization. The invention provides at least one detergent-insoluble heat-sensitive component of the perinuclear matrix of a spermatozoon (SOAFm) that acts coordinately with at least one heat-stable submembrane sperm component. SOAFm is solubilized in vitro (SOAFs) under reducing conditions similar to those encountered in the ooplasm. By the method of the invention, the failure of heat-inactivated demembranated sperm heads to activate an egg is rescued by coinsertion of SOAFs into an oocyte. SOAFs is protease-sensitive and is liberated from demembranated heads in a temperature-dependent manner that inversely correlates with the ability of demembranated sperm heads to activate oocytes.

Abstract: The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of malarial surface protein MSP-1 which is known to be difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred protein candidates for expression using the recombinant techniques of the invention are MSP-1 proteins expressed from DNA coding sequences comprising reduced overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the native MSP-1 gene.

Abstract: A gene is transferred to the early stage chicken embryo by electroporation with placing the electrode tips to hold both ends of the embryo. Transfer of the desired gene to the early stage embryo was detected using the &bgr;-galactosidase gene of E coli as a reporter gene. The expression of the gene in the early stage embryo of chicken was thus confirmed. This method for transferring a gene into undifferentiated cells is simple to implement, highly efficient in transferring a gene, and applicable to various animal species.

Abstract: Transgenic non-human animals are described comprising a transgene for a species-specific pathogen and transgene(s) for at least one receptor restricting infection of the pathogen to the host species. Also described is a method for creating the transgenic non-human animal of this invention and a method for screening an agent for the ability to inhibit infection by a species-specific virus using said transgenic non-human animal. The transgenic animal of this invention has a sustained productive viral infection and does not develop a virus-specific immune response, thereby resulting in an extremely useful self-contained system to investigate the factors modulating in vivo replication of human pathogens, the pathophysiological effect of pathogen replication and production, and the effectiveness of novel therapies and vaccines modifying or inhibiting the course of pathogenesis.

Abstract: The present invention provides a composition for targeted delivery of a nucleic acid to a cell comprising a biotinylated recombinant adenovirus, wherein biotin is covalently linked to the recombinant adenovirus, wherein the recombinant adenovirus comprises the nucleic acid, and wherein the recombinant adenovirus is linked via streptavidin to a biotinylated targeting moiety. Also provided by this invention is a method for targeted delivery of a nucleic acid to a selected cell in a subject comprising administering to the subject a composition comprising a biotinylated recombinant adenovirus, wherein biotin is covalently linked to the recombinant adenovirus, wherein the recombinant adenovirus comprises the nucleic acid, and wherein the recombinant virus is linked via streptavidin to a biotinylated targeting moiety that specifically targets the selected cell.

Abstract: The present invention discloses transgenic mice with inactivating mutations in the endogenous gene for the acetyl-CoA carboxylase-2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase-2 results in mice exhibiting a phenotype of reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fat oxidation, and reduced fat accumulation in the liver and fat storage cells. As a result, the mice consume more food but accumulate less fat and remain leaner than wild type mice fed the same diet. These results demonstrate that inhibition of ACC2 acetyl-CoA carboxylase could be used to regulate fat oxidation and accumulation for purposes of weight control. The transgenic mice of the instant invention provide a useful animal model to identify such inhibitors and for studying the mechanisms of fat metabolism and weight control.

Abstract: The present invention provides improved methods and compositions for the generation of transgenic non-human animals. The present invention permits the introduction of exogenous nucleic acid sequences into the genome of unfertilized eggs (e.g., pre-maturation oocytes and pre-fertilization oocytes) by microinjection of infectious retrovirus into the perivitelline space of the egg. The methods of the present invention provide an increased efficiency of production of transgenic animals with a reduced rate of generating animals which are mosaic for the presence of the transgene.

Abstract: A mouse is provided which is selectively deficient in natural killer cells. Also provided are methods for producing the mouse. Additionally, mice which are deficient in natural killer cells and B cells, natural killer cells and T cells, and natural killer cells, T cells, and B cells are provided, along with methods for making these mice. Methods of using these mice to: produce an animal containing human tissue, evaluate the effects of a composition on human tissue, determine whether a human disease is caused by a pathogenic agent, and study natural killer cells are also provided.

Abstract: The present invention relates to a viral vector system derived from Epstein-Barr Virus (EBV), where the transgene is effectively inserted into the EBV major internal repeat region (IR1) without adverse affect on EBV latent or lytic function. The vector of the invention can target and stably transform B-lymphocyte cells, both in culture and in vivo.

Abstract: In attempts to determine the cause of hypertriglyceridemia, a model animal was established. This model is useful to analyze on the relationship between food ingestion and hypertriglyceridemia. When backcrossing of the Watanabe heritable hyperlipidemic rabbit and the Japanese white rabbit, individual rabbits with high triglyceride values were identified. A novel hereditary postprandial hypertriglyceridemic rabbit, characterized by normal serum triglyceride values under conditions of fasting and high levels of serum triglyceride value by ingestion of food was thus obtained.

Abstract: The present invention features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised xenogeneic transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection.

Abstract: Process for producing mammals with defined genetic properties, particularly transgenic mammals. Animals which are derived completely from ES cells are obtained by injecting totipotent cells (embryonic stem cells or embryonic germ cells) genetically manipulated and cultured in vitro into tetraploid blastocysts and implanting the resulting embryo in a foster mother, in a single operation.