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.
Type:
Grant
Filed:
May 30, 1995
Date of Patent:
January 7, 1997
Assignee:
GenPharm International, Inc.
Inventors:
Paulus J. A. Krimpenfort, Antonius J. M. Berns
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.
Type:
Grant
Filed:
July 27, 1992
Date of Patent:
July 18, 1995
Assignee:
GenPharm International, Inc.
Inventors:
Paulus J. A. Krimpenfort, Antonius J. M. Berns
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.