TABLE 1.
Clinical phenotypes of NOD mice and mice lacking NF-κB subunits and a proteasome
| Murine knockout model [reference(s)] | Phenotypesa | NOD symptomatology |
|---|---|---|
| NF-κB | ||
| p50−/− (70, 72) | Low IL-6 levels | − |
| High IFN-β levels | +++ | |
| Defective LPS stimulation | +++ | |
| Impaired antibody production | − | |
| Increased susceptibility to bacterial infections | +++ | |
| Normal resistance to viral infections | +++ | |
| Abnormal Ig class switching | +++ | |
| p65−/− (5, 6, 37, 59) | Embryonic lethality | − |
| Liver apoptosis | − | |
| Low GM-CSF levels | − | |
| TNF-α-induced apoptosis | +++ | |
| Inactivation of CD40 | +++ | |
| p100/p52−/− (12) | Defective immunological response by B cells | +++ |
| Abnormal spleen architecture | +++ | |
| Defective B-cell education | +++ | |
| p50−/− p52−/− (24, 39) | Inactivation of GM-CSF | − |
| Inactivation of M-CSF | − | |
| Inactivation of IL-12 | − | |
| Inactivation of IL-10 | +++ | |
| High-level expression of IL-6 | +++ | |
| High-level expression of IFN-β | +++ | |
| High-level expression of IFN-γ | +++ | |
| Defective B-cell maturation | +++ | |
| Proteasome (LMP2−/−) (81) | Defective MHC class I antigen presentation | +++ |
| Defective CD8+-T-cell education | +++ |
a
Abbreviations: Ig, immunoglobulin; M-CSF, macrophage colony-stimulating factor.