Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g.

Abstract: The present invention provides methods for construction of recombinant Yeast Artificial Chromosomes ("YAC") by homologous recombination between YACs during meiosis. In particular, conditions are provided for the step of mating haploid cells and for the step of spore analysis that increase the frequency of spores containing the desired recombinant YAC. The methods find particular use in constructing recombinant YACs between YACs that are incompatible when co-propagated in a diploid and/or that share homology regions of less than about 50 kilobases. Linking YACs, methods of their construction, and methods of their use are provided that allow facile construction of a YAC containing two or more discontinuous regions of DNA.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies, i.e., antibodies encoded by immunoglobulin heavy and light chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, transgenes encoding unrearranged heterologous human immunoglobulin heavy and light chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: The invention relates to methods for intracellularly producing DNA segments by homologous recombination of smaller overlapping DNA fragments and transgenic mammalian cells and transgenic non-human mammals produced by such methods.

Abstract: Transgenic mice having a phenotype characterized by the substantial depletion of a mature lymphocytic cell type otherwise naturally occurring in the species from which the transgenic mouse is derived. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the lymphocytic cell type which is depleted. The transgene comprised is a DNA sequence encoding a lymphatic polypeptide variant which inhibits maturation of the lymphocytic cell type.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies of multiple isotypes. Heterologous antibodies are encoded by immunoglobulin heavy chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences that permit isotype switching of encoded unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g.

Abstract: Transgenic mice having a phenotype characterized by the substantial absence of mature T lymphocytes otherwise naturally occurring in said mice. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the T lymphocyte which is depleted. The transgene comprises a DNA sequence encoding a T cell receptor polypeptide variant which inhibits maturation of the T lymphocyte.

Abstract: Described is a method of targeting specific genes to the mammary gland which results in the efficient synthesis and secretion of biologically important molecules. Further, there is described as a composition of matter, a transgenic mammal having the ability to reproduce itself and being suitable for the secretion of biologically active agents into its milk. Additionally there is disclosed as a composition of matter, recombinant DNA gene complexes designed to integrate into a mammalian genome and to synthesize and secrete biological active agents into the milk. Furthermore methods of producing and using altered milk are disclosed.

Abstract: Methods are provided for determining the oncogenic potential of chemical compounds which utilizes a transgenic mouse predisposed to T-cell lymphomas. The transgenic mouse expresses a pim-1 oncogene and as a consequence is predisposed to the spontaneous onset of T-cell lymphomas. The oncogenic potential of a chemical compound is determined by administering a known dose of the chemical compound of interest to a pim-1 transgenic mouse. Thereafter, the transgenic mouse is monitored to detect the onset of a T-cell lymphoma. The time of onset of the T-cell lymphoma and the dosage of the chemical compound are compared to either the onset of spontaneous T-cell lymphomas in the pim-1 transgenic mouse or to the onset of a T-cell lymphoma in a pim-1 transgenic mouse which has been exposed to a known quantity of a carcinogenic agent. This provides an indication of the oncogenic potential of the chemical compound.

Abstract: Transgenic mice having a phenotype characterized by the substantial absence of mature T lymphocytes otherwise naturally occurring in said mice. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the T lymphocyte which is depleted. The transgene comprises a DNA sequence encoding a T cell receptor polypeptide variant which inhibits maturation of the T lymphocyte.