Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector

Immunology
C KardinalR Mocikat

Abstract

Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, r...Continue Reading

References

Sep 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·C R WoodR J Kaufman
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·H P FellK R Folger
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M D BakerM J Shulman
Oct 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·T L Orr-WeaverR J Rothstein
Mar 1, 1995·European Journal of Immunology·C KardinalR Mocikat

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Citations

Apr 5, 2007·Nature Protocols·Lei Wang, Roger Y Tsien
Aug 17, 2005·Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre·Abir A El-Abdallah, Christopher H J Ford
Nov 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Lei WangRoger Y Tsien

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