TABLE 2.
Changes to smooth muscle cells in mouse CNS AVM models.
| Genetic model | CNS location | Location of genetic manipulation | Genetic manipulation timepoint | Cellular characteristics of SMCs | Molecular characteristics of SMCs | Observed phenotype timepoint | AVM | References |
|---|---|---|---|---|---|---|---|---|
| Alk11flox/2flox | Brain | ECs | 8 weeks (Ad-Cre and AAV-VEGF injection) | /// | Decreased expression of αSMA | 16 weeks | Yes | Chen et al., 2013 |
| Alk12flox/2flox | Zhu et al. (2018) | |||||||
| Cdh5-CreERT2; Smad4flox/flox | Retina | ECs | P0, P1, P2 (tamoxifen injection) | Decreased arterial αSMA. Increased venous αSMA coverage | /// | P6 | Yes | Ola et al. (2018) |
| Retina | ECs | P1, P4 (tamoxifen injection) | Impaired vSMC coverage in veins and AVMS | Increased αSMA expression in veins and AVMs | P7 | Yes | Crist et al. (2018) | |
| Cdh5-CreERT2; Eng2flox/2flox | Retina | ECs | P2, P4 (tamoxifen injection for neonates) | Abnormal vSMC organization | Decreased expression of αSMA. | P6 | Yes (by P7) | Mahmoud et al. (2010) |
| Pdgfrβ-CreERT2; Rbpjflox/flox | Retina | PCs | P1, P2, P3 (injection to nursing mom or pups) | Decreased vSMC coverage of arteries | Increased αSMA expression in veins | P10, P14, 6 weeks | Yes | Nadeem et al. (2020) |
| Reduced vSMC coverage of arteries | No αSMA expression in veins | P5 | No | |||||
| Decreased αSMA expression in arteries | ||||||||
| Brain | PCs | P1, P2, P3 (tamoxifen injection) | Reduced vSMC coverge | Decreased expression of Acta2, Tagln | P10 | Yes | Diéguez-Huertado et al. (2019) | |
| Pdgfrβ-CreERT2; Notch1+/+; Notch3flox/flox | Retina | PCs | P1, P2, P3 (tamoxifen injection) | Reduced vSMC coverage | /// | P14 | Abnormal Vasculature (Increased vessel diameter) | Nadeem et al. (2020) |
| Pdgfrβ-CreERT2; Notch1flox/+; Notch3flox/flox | Yes | |||||||
| Pdgfrβ-CreERT2; Notch1flox/flox; Notch3flox/flox | Increased αSMA expression in veins | |||||||
| Pdgfrβ-CreERT2; dnMAMLflox/flox | Retina | PCs | P1, P2, P3 (tamoxifen injection) | Decreased vSMC coverage | /// | 6 weeks | Yes | Nadeem et al. (2020) |
| Pdgfrβ-CreERT2; Srfflox/flox | Retina | PCs and vSMCs | P1, P2, P3 (tamoxifen injection) | Hierarchical patterning defects. Dilated artery and veins. Reduced vascular bed, decreased vessel branch points | Decreased expression of αSMA(Acta2), Mhy11, Tagln, Myl9, Tpm2, Actc1, Actg1, Cacna1d, Cacna1f, Kcnma1, Kcnmb1 | P12 | Yes | Orlich et al. (2022) |
| Increased venous vSMC and decrased arterial vSMC coverage | ||||||||
| Reduced vSMC contractility | ||||||||
| SM22α-Cre; Alk1flox/flox | Brain, Spinal Cord | SMCs | with SM22α-Cre expression | Abnormal vSMC coverage | /// | 18–102 weeks | Yes | Milton et al. (2012) |
| SM22α-Cre; Alk1flox/- | ||||||||
| SM22α-Cre; Eng2flox/2flox | Brain, Spinal Cord | SMCs | with SM22α-Cre expression | /// | /// | 5 weeks | Yes | Choi et al. (2014) |
| Notch1+/−; Notch3−/− | Retina | Germline Deletion | Impaired vSMC differentiation | Decreased expression of αSMA | P5 | Abnormal Vasculature (AVMs at P13). Abnormal Vasculature | Kofler et al. (2015) | |
| Notch3−/− | ||||||||
EC, endothelial cell; PC, pericyte; Corr, corroborated; pSMAD3, phosphorylated SMAD;, Alk1, Acvrl1; Adenovirus-Cre, Ad-Cre; adeno-associated virus-VEGF, AAV-VEGF; ///, not reported or does not apply.