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. Author manuscript; available in PMC: 2022 Apr 26.
Published in final edited form as: Annu Rev Immunol. 2021 Mar 1;39:719–757. doi: 10.1146/annurev-immunol-093019-125918

Table 1.

Eosinophil-deficient mouse strains

Strain Construct mechanism Eosinophil levels Advantages Constraints/off target References
IL-5−/− and IL-5Rα−/− Knockout of IL-5 or IL-5Rα, which are important in eosinophil hematopoiesis, survival, and priming BM: normal
Blood: reduced
Tissues: reduced

  • Eosinophilia dramatically reduced upon systemic challenge (allergy or parasite)

  • Pathway is representative of eosinophils in humans

  • Incomplete eosinophil depletion

  • IL-5/IL-5Rα affects B-1 (CD5+) cells (mice), mast cells (mice), basophils, and likely some stromal cells

  • IgM and IgA low

  • Peyer patches small

 60–68
ΔdblGATA-1 Mutation in the GATA-1a cis-binding site needed for EoP development. Not to be confused with GATA-1 ΔneoΔHS/GATA-1low BM: deficient
Blood: deficient
Tissues: deficient

  • Complete eosinophil depletion

  • Normal breeding, general development, and life span

  • Impairment of basophil progenitors, basophil IL-4 production, mast cell numbers, and IgE activation

  • Red blood cells and hematocrit may be mildly reduced

  • Unknown additional transcription factor effects

 15, 71, 72, 261–263
MBP-1−/−/EPX−/− Double knockout of eosinophil granule proteins MBP-1 and EPX results in death of EoPs BM: deficient
Blood: deficient
Tissues: deficient

  • >95% eosinophil depletion

  • Highly eosinophil specific

  • Normal breeding, general development, life span

  • Unknown mechanism of cell death

 73
PHIL Transgenic mouse expressing DTA downstream of an EPX promoter BM: deficient
Blood: deficient
Tissues: deficient

  • Complete ablation of eosinophils

  • Highly eosinophil specific due to EPX promoter

  • Due to random integration into genome certain abnormalities in mice may occur

 70
iPHIL Knock-in of EPX promoter driving DTR (injection of DT targets eosinophils) BM: deficient
Blood: deficient
Tissues: deficient

  • Inducible depletion of eosinophils

  • Highly eosinophil specific due to EPX promoter

  • Normal breeding, general development, and life span

  • Only EoPs are targeted, as DTR does not appear to be expressed on differentiated eosinophils

  • Mice develop antibodies to DT after three weeks (tested with Cμ mice)

  • EPX fails to be expressed, so hemizygous iPHIL must be used

 74
eoCre Knock-in of EPX promoter driving expression of Cre (eosinophil-specific Cre)
Depletion occurs by crossing to ROSA-fl-stop-fl-DTA or ROSA-fl-stop-fl-hSiglec-8+αSiglec-8 treatment or Xbp1fl/fl 		BM: deficient
Blood: deficient
Tissues: deficient

  • Cre is 99% efficient when crossed to a ROSA floxed site

  • Validated with many floxed strains

  • Highly eosinophil specific due to EPX promoter

  • Normal breeding, general development, and life span

  • EPX fails to be expressed, so hemizygous eoCre must be used

  • Cre efficiency depends on availability of floxed gene, like any Cre/loxP system

 24, 52, 75, 76

Abbreviations: BM, bone marrow; Cre, Cre recombinase; DT, diphtheria toxin; DTA, diphtheria toxin A; DTR, diphtheria toxin receptor; eoCre, Epxtm1.1(cre)JLee; EoP, eosinophil progenitor; EPX, eosinophil peroxidase; iPHIL, Epxtm2.1(HBEGF)JLee; MBP-1, major basic protein 1; PHIL, Tg(EPO-DTA)#NAL.

a

Xbp1 and GATA-1 are transcription factors.