Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US5859307

Title:Mutant RAG-1 deficient animals having no mature B and T lymphocytes
Inventors:Mombaerts, Peter; Cambridge, MA, USA
Tonegawa, Susumu; Newton, MA, USA
Johnson, Randall S.; Boston, MA, USA
Papaioannou, Virginia; Lexington, MA, USA
Summary:Described herein is a novel homozygous RAG-1 deficient mouse having a homozygous mutation inserted into its endogenous RAG-1 gene by homologous recombination in embryonic stem cells such that the RAG-1 gene of the mouse is non-functional and does not express a functional RAG-1 protein, and wherein the mouse has no mature B and T lymphocytes. The invention relates to immunodeficient animals and their production via the introduction of a mutation in RAG-1 into the germline of the animals via gene targeting in embryonic stem cells. Claims of the invention include the arrest of B and T cell differentiation at an early stage which correlates to the inhibition of V(D)J recombination, resulting in mice which do not have mature B and T lymphocytes and which do not express immunoglobulin or T cell receptors. Also provided are methods by which the same strategy may be applied to the production of other RAG-1 deficient nonhuman mammals, such as rabbits, rats, and pigs, for the cultivation of human lymphocytes in the expression of human immunoglobulin. Therapeutic and experimental applications are included for the expansion of mammalian lymphocytes, for the establishment of continuous lymphoid cell lines, for crossbreeding with other animal lines, for the establishment of mammalian tumor models and for the study of immunodeficiency disorders.
Abstract:Immunodeficient animals are generated by introducing a mutation in RAG-1 into the germline of the animals via gene targeting in embryonic stem cells. The production of mutant RAG-1 deficient mice is detailed. RAG-1 deficient mice have no mature B and T lymphocytes. The arrest of B and T cell differentiation occurs at an early stage and correlates with the inability to perform V(D)J recombination. To date, these mice do not have mature B and T lymphocytes, nor do they express immunoglobulin or T cell receptors. The same strategy can be applied to the generation of other RAG-1 deficient animals, such as rabbits, rats, and pigs, using known techniques. These animals are all useful for the same general purposes as the scid mice, for example, cultivation of human lymphocytes for expression of human immunoglobulin. Other uses include the establishment of continuous lymphoid cell lines and, by crossbreeding with other lines of animals, the establishment of animals developing tumors for use in studying tumor cell developments and treatments.
US Patent Website:Click Here for Full Text of Patent
Title Number:US5859307
Application Number:US1994000254989
Date Filed:07/06/1994
Date Published:12/01/1999
Assignee:Massachusetts Institute of Technology, Cambridge, MA, USA Dana Farber Cancer Institute and Tufts University, Boston, MA, USA


 
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