Table 1.
Eosinophil-Attenuated Mouse Strains
| Eosinophil-Deficient Strains |
Genetic Modification |
Congenital or Inducible |
Mechanism of Ablation | Ablation of eosinophils (% relative to wild type) |
Eosinophil Specificity |
Considerations | REF | |
|---|---|---|---|---|---|---|---|---|
| Blood | BAL* | |||||||
| PHIL | Transgenic (plasmid) | Congenital | EPX-promoter driven expression of Diphtheria Toxin A (cell autonomous ablation) | >99% | >99% | YES | Transgenic insertion site is unknown | [40] |
| iPHIL | Knock-In | Inducible | EPX-promoter driven expression of human Diphtheria Toxin Receptor (injection of Diphtheria Toxin targets eosinophils) | >99% | >99% | YES | Can develop humoral resistance to DT with repeated injections over 3 weeks** Endogenous EPX expression is reduced Will not kill differentiated eosinophils, only progenitors. |
[45] |
| eoCRE (X) ROSA26flox-STOP-lox-DTA | Knock-In | Congenital | EPX-promoter driven expression of Cre recombinase. Cre cleaves out a floxed-stop codon to allow translation of Diphtheria Toxin A (cell autonomous ablation) | >99% | >99% | YES | Endogenous EPX expression is reduced | [46] |
| MBP-1−/−/EPX−/− | Knockout | Congenital | Deficiency in granule proteins MBP-1 and EPX leads to apoptosis of eosinophil progenitors (mechanism(s) unknown) | >90% | >80% | YES | A small percent of granule-free eosinophils differentiate in vivo, although the role of these eosinophils is unknown. | [138] |
| ΔdblGATA-1 | Knockout Functional Mutation | Congenital | Knockout mutation of a double GATA DNA binding site with the promoter of the GATA-1 transcription factor gene (GATA-1 is necessary for eosinophil hematopoiesis) | >99% | >99% | Mostly | Mice have anemia. Reduced basophil survival and IL-4 production. Eosinophils can be generated ex vivo Other roles for GATA-1 unknown. |
[42–44, 139, 140] |
| Eosinophil-Attenuated Strains | ||||||||
| epx DTR | Transgenic (BAC)*** | Inducible | EPX-promoter driven expression of human Diphtheria Toxin Receptor (injection of Diphtheria Toxin targets eosinophils) | <75% | ND | YES | Failure to reduce eosinophils by more than 25% in blood and spleen and no reduction in bone marrow. | [141] |
| IL-5−/− | Knockout | Congenital | Targeting of a cytokine significant to eosinophil hematopoiesis, survival and priming. | <20% | >90% | Mostly | Incomplete ablation and other cells may be affected by IL-5 deficiency. LDLN eosinophils remain functional. | [16, 78, 142, 143] |
| IL-5 Rα−/− | Knockout | Congenital | Targeting of a cytokine receptor significant to eosinophil hematopoiesis, survival and priming. | <50% | <10% | Mostly | Incomplete ablation and other cells may be affected by IL-5Rα deficiency | [144] |
| Eotaxin-1−/− | Knockout | Congenital | Targeting of a chemokine (CCL11) that binds CCR3 to induce recruitment into tissues. | 0% | <30% | Mostly | Incomplete ablation. Inhibits recruitment by eotaxin-CCR3 | [36] |
| Eotaxin-2−/− | Knockout | Congenital | Targeting of a chemokine (CCL24) that binds CCR3 to induce recruitment into tissues. | 0% | >70% | Mostly | Incomplete ablation. Inhibits recruitment by eotaxin-CCR3 interactions. | [39] |
| CCR3−/− | Knockout (Neo insert)£ | Congenital | Targeting of the chemokine receptor that binds eotaxins-1,-2, −3. | 0% | >50% | Mostly | Incomplete ablation. Inhibits recruitment by eotaxin-CCR3 interactions. CCR3 may be needed by other cells (e..g, mast cells). Elevated peripheral eosinophilia. | [38] |
| CCR3−/− | Knockout (LacZ insert) £ | Congenital | Targeting of the chemokine receptor that binds eotaxins-1,-2, −3. | 0% | >90% | Mostly | Incomplete ablation. Inhibits recruitment by eotaxin-CCR3 interactions. CCR3 may be needed by other cells (e.g., mast cells). Elevated peripheral eosinophilia. | [37] |
| IL-5−/−/Eotaxin-1 | Knockout | Congenital | Double knockout mice deficient in the cytokine IL-5 and the chemokine eotaxin-2 or eotaxin-1 | <10% | >90% | Mostly | Incomplete ablation. Inhibits recruitment by eotaxin-CCR3 interactions. Elevated peripheral eosinophilia. | [145] |
| Eotaxin-1/-2−/− | Knockout | Congenital | Double knockout mice deficient in the chemokines (CCL11 and CCL24) that bind CCR3 to induce recruitment into tissues. | 0% | >80% | Mostly | Incomplete ablation. Inhibits recruitment by eotaxin-CCR3 interactions. | [37, 52] |
| PIR-B−/− | Knockout | Congenital | Targeting of a paired immunoglobulin-like receptor necessary for survival in response to IL-5 | ~30% | >80% | No | PRI-B is also on myeloid cells. Role in eosinophils is novel. | [146] |
*
BAL eosinophils in an acute OVA allergy model of asthma;
**
iPHIL mice are on also available on Ig heavy chain deficient mice to avoid antibody responses to DT;
***
BAC construct is different EPX sequence than used in PHIL, iPHIL, and eoCRE;
£
Independently created models; ND; not determined