Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US5591669

Title:Transgenic mice depleted in a mature lymphocytic cell-type
Inventors:Krimpenfort, Paulus J. A.; Amsterdam, Netherlands
Berns, Antonius J. M.; Spaarndam, Netherlands
Summary:This invention introduces a transgenic nonhuman mammal which is depleted of mature lymphocytic cells, methods and uses thereof. Described herein are transgenic mice produced by a transgene which encodes a lymphatic polypeptide variant to inhibit formation, such that the transgenic mice exhibit 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. Further disclosed are properties and methods by which the phenotype of the transgenic mouse is characterized by a disruption of the expression of the C? and C? portions of the endogenous immunoglobulin heavy chain and an absence of plasma B cells which produce naturally occurring mouse antibodies, such that the phenotype is conferred by an immunoglobulin heavy chain targeting the transgene which is introduced into an ES target cell and integrated into somatic and germ cells of the tranegenic mouse or of an ancestor of the mouse by homologous recombination with a cognate endogenous immunoglobulin heavy chain allele. Further claims of the invention include a resulting targeted immunoglobulin heavy chain allele which is not expressed, wherein the immunoglobulin heavy chain targeting transgene comprises a stop codon as well as DNA sequences for the identification and selection of ES cells containing the transgene in the targeted allele and DNA sequences of a mouse heavy chain immunoglobulin gene having sufficient sequence homology to recombine with the endogenous allele in the ES target cell. Further disclosed are methods by which the deletion of nucleotides from the cognate endogenous immunoglobulin heavy chain allele comprises a deletion of J segments of the variable region. Therapeutic applications for the use of such transgenic mice in the treatment of human diseases are included. This invention represents a continuation of other applications filed by the same assignee and inventors.
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.
US Patent Website:Click Here for Full Text of Patent
Title Number:US5591669
Application Number:US1995000454034
Date Filed:30/05/1995
Date Published:07/01/1997
Assignee:GenPharm International, Inc., Palo Alto, CA, USA


 
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