Table 3.
Cell lineage-specific A20 alterations in mouse models that phenocopy human inflammatory and immune diseases
| Mutant type | Lineage/model | Phenotype | Refs |
|---|---|---|---|
| A20–/– | Global knockout mouse | Spontaneous systemic inflammation, severe cachexia and premature lethality; survival prolonged with Ripk1D138N/D138N or Ripk3–/– mice, but not with Mlkl–/– | 156,218,219 |
| A20−/− | Murine embryonic fibroblasts | Sensitized to RIPK1-dependent apoptosis and necroptosis | 38 |
| A20EKO | Keratinocyte-specific knockout mouse | Systemic inflammation and exacerbated disease in models of psoriasis and atopic dermatitis | 220 |
| A20LysM-Cre | Myeloid-specific knockout mouse | Spontaneous inflammatory joint arthritis; rescued by Ripk1D138N/D138N mutation, Ripk3–/– or Mlkl–/– | 80,208 |
| A20IEC/myel-DKO | IEC and myeloid-specific double-knockout mouse | Intestinal pathology through synergistic IEC and myeloid mechanisms to promote ileitis and severe colitis | 81 |
| A20mZnF7/mZnF7 | Global C764A;C767A ZnF7 knock-in mouse | Spontaneous inflammatory arthritis with activated RIPK1 | 80 |
| A20ΔIEC | IEC-specific knockout mouse | Hypersensitive to TNF-induced systemic inflammation; partially blocked by inhibition of RIPK1 (Ripk1D138N/D138N) | 221 |
| A20IEC-transgenic mice | IEC-specific overexpression | Hypersensitive to TNF-induced intestinal damage in RIPK1-dependent manner | 79 |
IEC, intestinal epithelial cell; MLKL, mixed-lineage kinase domain-like pseudokinase; RIPK1, receptor-interacting serine/threonine-protein kinase 1; TNF, tumour necrosis factor; ZnF7, zinc finger 7.