Key genetic and epigenetic modifiers encoded on chr. 22q11.2
| Gene name (protein name if coding) . | Gene function . | Mechanism of action . | Clinical phenotypes . | Comparative mouse modelsa . |
|---|---|---|---|---|
| TBX1 (T-box transcription factor 1) | Transcription factor | Binds DNA sequences and associates with histone methyltransferases to activate transcription | Multiple and variable congenital defects (see Table 1) | KOb is embryonic lethal Haploinsufficiency: Similar phenotypes as humans but much less penetrant thymic hypoplasia |
| CRKL (CRK-like) | SH2 and SH3 domain containing intracellular signaling adapter protein | Promotes intracellular signal transduction | Genetic modifier of 22q11.2DS | KO is prenatal lethal with heart, liver, and placental defects Crkl+/−Tbx1+/− mice: CHDc and thymic hypoplasia |
| CLDN 5 (CLAUDIN 5) | Tight junction protein | Blood–brain barrier (BBB) integrity Cortical thymus–blood barrier | Increased vascular permeability and weakened BBB | Mouse KO leads to nonviable offspring due to defective BBB |
| DGCR6 (DGCR6) | Nuclear phosphoprotein | Expressed in neural crest cells Homology to laminin-g1 chain | CHD with deletion or duplication | Haplosufficiency associated with learning deficit |
| DGCR8 (DGCR8) | MicroRNA processing enzyme | Required for miRNA biogenesis | Processing microRNAs in immune cells and neural progenitors | KO is embryonic lethal at E6.5 |
| MiR-185 | MicroRNA | Targets SERCA2, BTK, MZB1, NFAT, CAM4K | Potential contributor to autoantibody production | KO is normal: Increased bone formation during osteogenesis Haploinsufficiency correlated with increased autoantibody |
| DGCR5 | LncRNA | Regulator of alternative splicing | Unknown | No mouse model |
| Gene name (protein name if coding) . | Gene function . | Mechanism of action . | Clinical phenotypes . | Comparative mouse modelsa . |
|---|---|---|---|---|
| TBX1 (T-box transcription factor 1) | Transcription factor | Binds DNA sequences and associates with histone methyltransferases to activate transcription | Multiple and variable congenital defects (see Table 1) | KOb is embryonic lethal Haploinsufficiency: Similar phenotypes as humans but much less penetrant thymic hypoplasia |
| CRKL (CRK-like) | SH2 and SH3 domain containing intracellular signaling adapter protein | Promotes intracellular signal transduction | Genetic modifier of 22q11.2DS | KO is prenatal lethal with heart, liver, and placental defects Crkl+/−Tbx1+/− mice: CHDc and thymic hypoplasia |
| CLDN 5 (CLAUDIN 5) | Tight junction protein | Blood–brain barrier (BBB) integrity Cortical thymus–blood barrier | Increased vascular permeability and weakened BBB | Mouse KO leads to nonviable offspring due to defective BBB |
| DGCR6 (DGCR6) | Nuclear phosphoprotein | Expressed in neural crest cells Homology to laminin-g1 chain | CHD with deletion or duplication | Haplosufficiency associated with learning deficit |
| DGCR8 (DGCR8) | MicroRNA processing enzyme | Required for miRNA biogenesis | Processing microRNAs in immune cells and neural progenitors | KO is embryonic lethal at E6.5 |
| MiR-185 | MicroRNA | Targets SERCA2, BTK, MZB1, NFAT, CAM4K | Potential contributor to autoantibody production | KO is normal: Increased bone formation during osteogenesis Haploinsufficiency correlated with increased autoantibody |
| DGCR5 | LncRNA | Regulator of alternative splicing | Unknown | No mouse model |