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 present invention provides novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The present invention also provides for the transgenic animals which contain these recombinant nucleic acid vectors. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. According to various embodiments of the invention, the vectors may be used to create transgenic animals or to transfect cells in culture. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.-globin protein in erythroid tissues, including red blood cells.

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 .beta.-globin locus are sufficient to result in high level expression of human .alpha.- or .beta.-globin transgenes. The present invention also provides for novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.

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 .beta.-globin locus are sufficient to result in high level expression of human .alpha.- or .beta.-globin transgenes. The present invention also provides for novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.

Abstract: Mammalian genes that encode hormones are cloned and linked to strong promoter DNA sequences. The linked sequences are inserted in plasmids for amplification in prokaryotic cells, and multiple copies of the linked sequences are excised therefrom. Linked sequences are subsequently microinjected into fertilized eggs and the fertilized eggs are implanted into pseudo-pregnent females of the same species. As a result, transgenic animals are born having the linked sequences incorporated into their genomes and expressing the gene-encoded hormone. Because multiple copies of the linked sequences are frequently inserted and because production of the hormone is not limited to certain organs, as is the case with most endogenous hormones, the transgenic animals produce substantial amounts of the hormone. Hormone can be harvested from the living animal (and from its hormone-producing progeny) by extracting fluid, such as blood serum or ascites fluid, on a regular basis.

Abstract: The transcription of DNA sequences in living cells is subjected to external regulation by incorporation of promoter/regulator DNA sequences responsive to metals and/or steroids. More particularly, regulation of the transcription of selected exogenous DNA sequences incorporated into eukaryotic host cells is facilitated by operative association (e.g., fusion) of the selected sequence to a promoter/regulator DNA sequence which is positively or negatively responsive to environmental variation in the concentration of heavy metal ions and/or steroid hormones. As an example, a structural gene for thymidine kinase from herpes simplex virus, fused to the promoter/regulator DNA sequence of a mouse metallothionein-I gene and incorporated on a suitable DNA plasmid vector, is introduced into mouse embryos and stably incorporated therein.