Abstract: A synthetic polynucleotide and a method are disclosed for selectively expressing a protein in a target cell or tissue of a mammal. Selective expression is effected by replacing at least one existing codon of a parent polynucleotide encoding a protein of interest with a synonymous codon to produce a synthetic polynucleotide having altered translational kinetics compared to the parent polynucleotide. The synonymous codon is selected such that it has a higher translational efficiency in the target cell or tissue relative to one or more other cells or tissues of the mammal.

Abstract: Transgenic nonhuman mammals, such as transgenic mice, which lack erythropoietin expression, in which the erythropoietin receptor is deleted, which carry a heterologous erythropoietin receptor (e.g., a chimeric receptor); constructs useful for producing such transgenic nonhuman mammals, embryonic stem cells containing the constructs, a method of producing the transgenic nonhuman mammals and a method of identifying erythropoietin mimics or mimetics.

Abstract: Novel forms of vascular endothelial growth factor genes and the novel proteins encoded by these genes are disclosed. More particularly, novel forms of human VEGF-A which contain exon 6b and do not contain exon 6a are disclosed. Other novel forms of human VEGF-A contain exon 6b in addition to exon 6a. These novel forms of VEGF-A include VEGF-A138, VEGF-A162, and VEGF-A182. Such novel VEGF proteins may be used in treatment of the cardiovascular system and its diseases through effects on anatomy, conduit function, and permeability, and more particularly in the treatment of cardiovascular disease by stimulating vascular cell proliferation using a growth factor, thereby stimulating endothelial cell growth and vascular permeability. The invention also relates to nucleic acids encoding such novel VEGF proteins, cells, tissues and animals containing such nucleic acids; methods of treatment using such nucleic acids; and methods relating to all of the foregoing.

Abstract: The present invention relates to genes, referred to herein as cell death-protective genes, which protect cells against programmed cell death by antagonizing the activities of genes which cause cell death. As described herein, a cell death-protective gene from the nematode Caenorhabditis elegans, called ced-9, has been identified, sequenced, and characterized. ced-9 is essential for C. elegans development and apparently functions by protecting cells which normally live during development from programmed cell death. Mutations which constitutively activate and inactivate the ced-9 gene are also described. ced-9 was shown to function by antagonizing the activities of the cell death genes, ced-3 and ced-4. As further described, the protein product of the human oncogene bcl-2 was found to have a similar sequence to the ced-9 protein.

Abstract: Congenic animals and animal populations having type II diabetes-associated phenotypes are described. Insulin degradation polypeptides having amino acid substitutions linked to a type II diabetes-associated phenotypes also are described.

Abstract: The present invention describes a non-human transgenic mammal that produces in its leukocytes, a recombinant human leukotriene B4 receptor (BLTR), having physiological activity of human BLTR. The transgenic mammal has stably integrated into its genome an exogenous gene construct which includes (A) 5′ expression regulating sequences, including a BLTR specific promoter, (B) DNA encoding the BLTR and a signal sequence effective in directing overexpression of the BLTR into leukocytes of the transgenic mammal and (C) 3′ regulatory sequences that result in the overexpression of the DNA in the leukocytes. In one embodiment, (A), (B), and (C) are operably linked in the gene construct to obtain production of the BLTR in the leukocytes and overexpression thereof in the transgenic mammal.

Abstract: The present invention relates to a human type-5 recombinant adenovirus vector for achieving cardiac restricted transcription involving utilization of the cardiomyocyte-restricted cardiac ankyrin repeat protein (CARP) promoter with inclusion of the inverted terminal repeat sequences from human adeno-associated virus (AAV). Using green fluorescent protein (GFP) as a marker gene, the recombinant adenovirus vector (Ad/CG/ITR) is shown to direct transgene expression to myocardial tissue in vivo and in vitro in mouse models.

Abstract: An animal, e.g., transgenic mouse, in which the MSH5 gene is misexpressed. The animal is useful for screening treatments for a number of conditions. Methods for identifying contraceptive agents are also described.

Abstract: The present invention relates to a method of identifying drugs or agents which have immuno-suppressive effects through or as a result of their effect on calcineurin, including drugs which affect the calcineurin A&agr; (CNA&agr;) subunit or the calcineurin A&bgr; (CNA&bgr;) subunit. In addition, the present invention relates to a method of identifying drugs which reduce (partially or totally) phosphorylation of the microtubule-associated protein tau, in the nervous system of a mammal; a method of identifying drugs which reduce (partially or totally) paired helical filament formation in the nervous system of a mammal; and a method of identifying drugs which reduce (partially or totally) formation of paired helical filaments, amyloid deposits or both. The present invention also relates to transgenic non-human mammals, such as rodents and particularly mice, which lack a functional calcineurin gene and, thus, have disyrupted calcineurin expression.

Abstract: The present invention relates to calcium channel compositions and methods of making and using same. In particular, the invention relates to calcium channel alpha2delta (&agr;2&dgr;) subunits and nucleic acid sequences encoding them. These compositions are useful in methods for identifying compounds that modulate the activity of calcium channels and for identifying compounds as therapeutic for disease.

Abstract: A method for screening substances for oncogenic activity is disclosed. The method involves administering the substance to an animal lacking responsiveness to interferon&ggr; and detecting a higher frequency or earlier time of tumor formation in the test animal compared to control animals. In addition, a method is provided for predicting the aggressiveness of a tumor in a patient.

Abstract: A method for obtaining a eukaryotic cell transfected with an episome involves transfecting the cell with the episome under conditions wherein cells survive that are successfully transfected with the episome. The resulting cells express both a first protein whose expression causes cell death and a second protein whose expression prevents cell death resulting from expression of the first protein.

Abstract: Nonobese Diabetic Mice (NOD mice) that do not develop diabetes may be bred to produce F1 offspring that develop a condition that closely mimics rheumatoid arthritis (RA) in humans. The RA-like disease in the F1 mice, designated NOD-RA mice, is similar to human RA in clinical, radiological, histological and serological characteristics. The parents (F0) and their progeny (F1) are not diabetic and never develop hyperglycemia, and the parental mice (F0) do not themselves exhibit any symptoms of the RA-like condition that afflicts some of their progeny. The incidence, penetrance, gender domination, progression, and lifelong exacerbation of symptoms after pregnancy shown in the RA-like condition afflicting NOD-RA mice are all comparable to phenomena observed in the human disease. The NOD-RA mice provide a new spontaneous model of human RA that will be useful for studying rheumatoid arthritis and testing new drugs and reagents for treating or diagnosing the disease.

Abstract: A transgenic non-human animal with alterations in the osteopontin gene is prepared by introduction of a gene encoding an altered osteopontin protein into a host non-human animal. Methods for using transgenic mice so generated to screen for agents that effect osteopontin's cellular modulating activity are also provided.

Abstract: The present invention details methods for the treatment of cancer. In particular, it concerns the induction of apoptosis of cancer cells following treatment with methoxyestradiol. 2-methoxyestradiol (2-MeOE2) increase wild-type p53 levels in a human non-small lung cancer cell lines associated with accumulation of cyclin dependent kinase inhibitor p21 WAF1/CIP1. Significant apoptotic cell death occurred after the drug treatment. Thus, 2-MeOE2 facilitates induction of p53-mediated apoptosis.

Abstract: Switch regions derived from an immunoglobulin (Ig) gene are used to direct recombination between a targeting construct containing a promoter, a switch region (S1), and 2) a target locus minimally containing a promoter, a switch region (S2), and a target sequence.

Abstract: An isolated DNA encoding the enzyme I-SceI is provided. The DNA sequence can be incorporated in cloning and expression vectors, transformed cell lines and transgenic animals. The vectors are useful in gene mapping and site-directed insertion of genes.

Abstract: A novel human sodium phosphate cotransporter expressed on the apical surface of intestinal epithelial cells (huNpt2B) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting Npt2B activity in a host and methods of treating disease conditions associated with Npt2B activity.

Abstract: Coinjection of unfertilized mouse oocytes with sperm heads and exogenous nucleic acid encoding a transgene results in transgene-expressing embryos, reflecting nucleic acid-sperm head association before coinjection. Nonselective transfer to surrogate mothers of embryos resulting from coinjection produced offspring expressing the integrated transgene.

Abstract: This invention provides an isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of the DNA regulates bone growth. This invention provides a polypeptide encoded by the isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of the DNA regulates bone growth. This invention also provides a polypeptide which comprise the portion of the mutated collagen X capable of regulating bone growth. This invention further provides a transgenic animal comprising an isolated DNA comprising the sequence which codes for a mutated collagen X or a portion thereof wherein the expression of the DNA regulates bone growth.