title: Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils.
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 Cre-mediated toxicity. The efficiency and specificity of Cre expression in eoCRE mice were demonstrated further in a cross with a knock-in mouse containing a "(flox-stop-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.
authors: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
authors: Alfred D
authors: AD
authors: Doyle
authors: Elizabeth A
authors: EA
authors: Jacobsen
authors: Sergei I
authors: SI
authors: Ochkur
authors: Lian
authors: L
authors: Willetts
authors: Kelly
authors: K
authors: Shim
authors: Joseph
authors: J
authors: Neely
authors: Jake
authors: J
authors: Kloeber
authors: Will E
authors: WE
authors: Lesuer
authors: Ralph S
authors: RS
authors: Pero
authors: Paige
authors: P
authors: Lacy
authors: Redwan
authors: R
authors: Moqbel
authors: Nancy A
authors: NA
authors: Lee
authors: James J
authors: JJ
authors: Lee
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000502:physiology*; D004804:Eosinophils / Q000201:enzymology*; D005434:Flow Cytometry; D059765:Homologous Recombination; D006801:Humans; D019426:Integrases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D047209:Eosinophil Peroxidase; C045073:Cre recombinase; D019426:Integrases
keywords: EPX; eosinophil granule protein; eosinophil lineage-specific knock-out; knock-in mice
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