Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6264915

Title:Process for detecting potential carcinogens
Inventors:Schiestl, Robert H.; Boston, MA, USA
Summary:This invention describes a process for screening the effect of an agent on genome rearrangement frequency in pregnant transgenic nonhuman mammals having a head-to-tail duplication of genetic elements in their genomes. Described herein are methods by which genetic elements are inserted into the haploid genome of a transgenic mouse, such that the repeated genetic elements are sufficiently homologous so that, under ambient conditions, they recombine with each other and give rise to an identifiable genome rearrangement at a rate of approximately 1x10-11 or more occurrences per cell per generation. Further described is the process by which at least one of the transgenic mice is exposed to the agent to be tested, from which one may determine the extent of the genome rearrangement which exists in a first exposed mouse selected from the group consisting of the exposed mouse, its offspring, and mixtures thereof. Comparisons are then made on the extent of genome rearrangement existing in the first mouse with the extent of genome rearrangement existing in a second unexposed mouse and the offspring of the unexposed control mice, and mixtures thereof. Also provided are applications and uses of such a procedure in the identification of potential carcinogens.
Abstract:A process for screening an agent to determine its effect upon the frequency of genome rearrangement in transgenic mammals. The process comprises the steps of: (a) providing a transgenic mammal into which repeated genetic elements have been inserted into its haploid genome. The repeated genetic elements are sufficiently homologous so that, under ambient conditions, they recombine with each other and give rise to an identifiable genome rearrangement at a rate of at least about 1.times.10.sup.-11 occurrences per cell per generation. In a preferred embodiment the rearrangement can be identified as a phenotypic event or by PCR. The process further comprises (b) exposing at least one of the transgenic mammals to the agent to be tested, thereby providing an exposed mammal and (c) determining the extent of genome rearrangement which exists in a first exposed animal selected from the group consisting of the exposed mammal, its offspring, and mixtures thereof. The process then (d) compares the extent of genome rearrangement existing in the first animal with the extent of genome rearrangement existing in a second unexposed mammal and the offspring of the unexposed control mammals, and mixtures thereof.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6264915
Application Number:US1997000958054
Date Filed:27/10/1997
Date Published:24/07/2001
Assignee:The President and Fellows of Harvard College, Cambrige, MA, USA


 
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