Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils

Alfred D. Doyle, Elizabeth A. Jacobsen, Sergei I. Ochkur, Lian Willetts, Kelly Shim, Joseph Neely, Jake Kloeber, Will E. LeSuer, Ralph S. Pero, Paige Lacy, Redwan Moqbel, Nancy A. Lee, James J. Lee

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Eosinophils are generally linked to innate host defense against helminths, as well as the pathologies associated with allergic diseases, such as asthma. Nonetheless, the activities of eosinophils remain poorly understood, which in turn, has prevented detailed definitions of their role(s) in health and disease. Homologous recombination in embryonic stem cells was used to insert a mammalianized Cre recombinase in the ORF encoding Epx. This knock-in strategy overcame previous inefficiencies associated with eosinophil-specific transgenic approaches and led to the development of a knock-in strain of mice (eoCRE), capable of mediating recombination of "floxed" reporter cassettes in >95% of peripheral blood eosinophils. We also showed that this Cre expression was limited exclusively to eosinophil- lineage committed cells with no evidence of Cremediated toxicity. The efficiency and specificity of Cre expression in eoCRE mice were demonstrated further in a cross with a knock-in mouse containing a "(floxstop- flox)" DTA cassette at the ROSA26 locus, generating yet another novel, eosinophil-less strain of mice. The development of eoCRE mice represents a milestone in studies of eosinophil biology, permitting eosinophil- specific gene targeting and overexpression in the mouse as part of next-generation studies attempting to define eosinophil effector functions.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalJournal of Leukocyte Biology
Volume94
Issue number1
DOIs
StatePublished - Jul 2013

Keywords

  • EPX
  • Eosinophil granule protein
  • Eosinophil lineagespecific knock-out
  • Knock-in mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Doyle, A. D., Jacobsen, E. A., Ochkur, S. I., Willetts, L., Shim, K., Neely, J., Kloeber, J., LeSuer, W. E., Pero, R. S., Lacy, P., Moqbel, R., Lee, N. A., & Lee, J. J. (2013). Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils. Journal of Leukocyte Biology, 94(1), 17-24. https://doi.org/10.1189/jlb.0213089