| First Author | Li J | Year | 2017 |
| Journal | Hum Mol Genet | Volume | 26 |
| Issue | 15 | Pages | 2949-2960 |
| PubMed ID | 28486600 | Mgi Jnum | J:243427 |
| Mgi Id | MGI:5908480 | Doi | 10.1093/hmg/ddx183 |
| Citation | Li J, et al. (2017) Sclt1 deficiency causes cystic kidney by activating ERK and STAT3 signaling. Hum Mol Genet 26(15):2949-2960 |
| abstractText | Ciliopathies form a group of inherited disorders sharing several clinical manifestations because of abnormal cilia formation or function, and few treatments have been successful against these disorders. Here, we report a mouse model with mutated Sclt1 gene, which encodes a centriole distal appendage protein important for ciliogenesis. Sodium channel and clathrin linker 1 (SCLT1) mutations were associated with the oral-facial-digital syndrome (OFD), an autosomal recessive ciliopathy. The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly. Sclt1-loss decreases the number of cilia in kidney; increases proliferation and apoptosis of renal tubule epithelial cells; elevates protein kinase A, extracellular signal-regulated kinases, SMAD and signal transducer and activator of transcription 3 (STAT3) pathways; and enhances pro-inflammation and pro-fibrosis pathways with disease progression. Embryonic kidney cyst formation of Sclt1-/- mice was effectively reduced by an anti-STAT3 treatment using pyrimethamine. Overall, we reported a new mouse model for the OFD; and our data suggest that STAT3 inhibition may be a promising treatment for SCLT1-associated cystic kidney. |
