Table 2.
List of mice models in linking NF-κB to autoimmunity.
| Gene (protein) | Mutations | Phenotype | Refs |
|---|---|---|---|
|
TNAIP3 (A20) |
-/- | lethal autoimmune disease | (167) |
| B cell-specific deletion of A20 | hyperesponsiveness of B cells and autoimmune disease with homologies to SLE | (168) | |
| dendritic cells-specific deletion of A20 | enhanced activation of cDCs and moDCs. development of organ-specific autoimmunity but not systemic autoimmunity. | (169) | |
| myeloid cells-specific deletion of A20 | intestinal pathology and cancer | (170) | |
| hematopoietic cells-specific deletion of A20 | severe inflammation accompanied by B lymphocytes apoptosis | (171) | |
| epithelial intestinal cells-specific deletion of A20 | dextran-sodium sulfate-induced colitis | (169) | |
| liver parenchymal cells-specific deletion of A20 | chronic liver inflammation | (144) | |
| haplo-insufficient A20-/- mice | psoriasis-like skin lesions associated with interleukin (IL)-17 and IL-23 overproduction | (172) | |
| A20-/- and A20-deficiency in astrocytes | neuroinflammation increase EAE disease severity |
(173, 174) | |
| CYLD | -/- | - T cell developmental defects and mice exhibit fewer mature CD4+ and CD8+ single positive thymocytes and peripheral T cells. - skin tumor development. - infection by S. pneumoniae infection - increase susceptibility to colitis-associated tumorigenesis following administration dextran sulfate sodium (DSS) |
(175) |
| B cells-specific deletion of CylD | no exacerbation of the developmental and activation defects of A20-deficient B cells | (129, 176–178) | |
| NKT cells-specific deletion of CylD | constitutive NF-κB activation responsible of a reduction of IL-7 secretion and ICOS expression | (178) | |
| skin-specific deletion of CylD | skin tumors after application of DMBA/TPA | (179) | |
| FAM105B (OTULIN) | -/- | embryonic lethality | (180) |
| inducible deletion of OTULIN in various lymphoid organs (spleen, thymus) | death of mice even in the adult state | (125) | |
| Bone marrow reconstitution experiments with inducibly depleted cells for OTULIN | - increase in neutrophils and cytokine secretion (TNF-IL-6, G-CSF) leading to systemic inflammation and autoimmunity - TNF neutralizing antibodies rescued the phenotype |
(125) | |
| myeloid cells-specific deletion of OTULIN | - inflammatory phenotype - increased serum levels of inflammation-associated cytokines and chemokines. Mice develop splenomegaly and autoimmunity |
(125) | |
| RBCK1 (HOIL-1) | -/- | polyglucosan body myopathy in old age | (154) |
| -/- and TNF-/-, TNFR1-/-, RIPK3 -/- or Caspase 8-/- | - lethality mainly due to deregulation of TNFR1-mediated cell death. - Ripk3-/-Caspase 8-/- HOIL-1-/- embryos suffer from intrinsic defects in early hematopoiesis |
(181) | |
| RNF31 (HOIP) | Transgenic expressing Deletion N-ter UBL HOIP | embryonic lethality at midgestational stage due to thoraco abdominal hemorrhages and vascular defects in embryo | (182) |
| keratinocyte-specific deletion of HOIP and HOIL-1 | severe dermatitis caused by TNFR1-induced, caspase-8-mediated apoptosis | (183) | |
| SHARPIN | -/- SHARPIN -/- and TNF-/- |
severe autoinflammatory disease (severe dermatitis and system-wide organ inflammation) and immunodeficiency rescued by TNF-/- | (23, 64, 184) |