| First Author | Yu J | Year | 2020 |
| Journal | J Cell Physiol | Volume | 235 |
| Issue | 1 | Pages | 210-220 |
| PubMed ID | 31188489 | Mgi Jnum | J:293676 |
| Mgi Id | MGI:6453442 | Doi | 10.1002/jcp.28960 |
| Citation | Yu J, et al. (2020) An antibody to Notch3 reverses the skeletal phenotype of lateral meningocele syndrome in male mice. J Cell Physiol 235(1):210-220 |
| abstractText | Lateral meningocele syndrome (LMS), a genetic disorder characterized by meningoceles and skeletal abnormalities, is associated with NOTCH3 mutations. We created a mouse model of LMS (Notch3(tm1.1Ecan) ) by introducing a tandem termination codon in the Notch3 locus upstream of the proline (P), glutamic acid (E), serine (S) and threonine (T) domain. Microcomputed tomography demonstrated that Notch3(tm1.1Ecan) mice exhibit osteopenia. The cancellous bone osteopenia was no longer observed after the intraperitoneal administration of antibodies directed to the negative regulatory region (NRR) of Notch3. The anti-Notch3 NRR antibody suppressed the expression of Hes1, Hey1, and Hey2 (Notch target genes), and decreased Tnfsf11 (receptor activator of NF Kappa B ligand) messenger RNA in Notch3(tm1.1Ecan) osteoblast (OB) cultures. Bone marrow-derived macrophages (BMMs) from Notch3(tm1.1Ecan) mutants exhibited enhanced osteoclastogenesis in culture, and this was increased in cocultures with Notch3(tm1.1Ecan) OB. Osteoclastogenesis was suppressed by anti-Notch3 NRR antibodies in Notch3(tm1.1Ecan) OB/BMM cocultures. In conclusion, the cancellous bone osteopenia of Notch3(tm1.1Ecan) mutants is reversed by anti-Notch3 NRR antibodies. |
