| First Author | Daoud F | Year | 2021 |
| Journal | Cell Mol Gastroenterol Hepatol | Volume | 11 |
| Issue | 2 | Pages | 623-637 |
| PubMed ID | 32992050 | Mgi Jnum | J:331135 |
| Mgi Id | MGI:6719881 | Doi | 10.1016/j.jcmgh.2020.09.014 |
| Citation | Daoud F, et al. (2021) Inducible Deletion of YAP and TAZ in Adult Mouse Smooth Muscle Causes Rapid and Lethal Colonic Pseudo-Obstruction. Cell Mol Gastroenterol Hepatol 11(2):623-637 |
| abstractText | BACKGROUND & AIMS: YAP (Yap1) and TAZ (Wwtr1) are transcriptional co-activators and downstream effectors of the Hippo pathway, which play crucial roles in organ size control and cancer pathogenesis. Genetic deletion of YAP/TAZ has shown their critical importance for embryonic development of the heart, vasculature, and gastrointestinal mesenchyme. The aim of this study was to determine the functional role of YAP/TAZ in adult smooth muscle cells in vivo. METHODS: Because YAP and TAZ are mutually redundant, we used YAP/TAZ double-floxed mice crossed with mice that express tamoxifen-inducible CreER(T2) recombinase driven by the smooth muscle-specific myosin heavy chain promoter. RESULTS: Double-knockout of YAP/TAZ in adult smooth muscle causes lethality within 2 weeks, mainly owing to colonic pseudo-obstruction, characterized by severe distension and fecal impaction. RNA sequencing in colon and urinary bladder showed that smooth muscle markers and muscarinic receptors were down-regulated in the YAP/TAZ knockout. The same transcripts also correlated with YAP/TAZ in the human colon. Myograph experiments showed reduced contractility to depolarization by potassium chloride and a nearly abolished muscarinic contraction and spontaneous activity in colon rings of YAP/TAZ knockout. CONCLUSIONS: YAP and TAZ in smooth muscle are guardians of colonic contractility and control expression of contractile proteins and muscarinic receptors. The knockout model has features of human chronic intestinal pseudo-obstruction and may be useful for studying this disease. |
