Limitations of cell-lineage-specific non-dynamic gene recombination in CD11c.Cre+ITGA4fl/fl mice

Navid Manouchehri, Rehana Z. Hussain, Petra D. Cravens, Richard Doelger, Benjamin M. Greenberg, Darin T. Okuda, Thomas G. Forsthuber, Todd N Eagar, Olaf Stüve

Research output: Contribution to journalArticle

Abstract

Background: The Cre-lox system is a non-dynamic method of gene modification and characterization. Promoters thought to be relatively cell-specific are utilized for generation of cell-lineage-specific gene modifications. Methods: CD11c.Cre+ITGA4fl/fl mice were generated to abolish the expression of ITGA (α4-integrin) in CD11c+ cells. Ex vivo flow cytometry studies were used to assess the expression of cellular surface markers in different lymphoid compartments and leukocytes subsets after Cre-mediated recombination. Results: A significant reduction of α4-integrin expression among CD11c+− cells was achieved in CD11c.Cre+ITGA4fl/fl mice in primary and secondary lymphoid tissues. A similar reduction in the expression of α4-integrin was also observed in CD11c cells. Conclusion: Cre-lox-mediated cell lineage-specific gene deletion is limited by the transient expression of recombination regulating sequences in hematopoietic cell lines. These methodological issues indicate the need to consider when to employ non-dynamic DNA recombination models in animal models of CNS autoimmunity. An experimental algorithm to address the biological complexities of non-dynamic gene recombination is provided.

Original languageEnglish (US)
Article number577245
JournalJournal of Neuroimmunology
Volume344
DOIs
StatePublished - Jul 15 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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