| First Author | Weinstein MM | Year | 2014 |
| Journal | J Bone Miner Res | Volume | 29 |
| Issue | 8 | Pages | 1815-1822 |
| PubMed ID | 24644033 | Mgi Jnum | J:233234 |
| Mgi Id | MGI:5781030 | Doi | 10.1002/jbmr.2220 |
| Citation | Weinstein MM, et al. (2014) Mice expressing mutant Trpv4 recapitulate the human TRPV4 disorders. J Bone Miner Res 29(8):1815-22 |
| abstractText | Activating mutations in transient receptor potential vanilloid family member 4 (Trpv4) are known to cause a spectrum of skeletal dysplasias ranging from autosomal dominant brachyolmia to lethal metatropic dysplasia. To develop an animal model of these disorders, we created transgenic mice expressing either wild-type or mutant TRPV4. Mice transgenic for wild-type Trpv4 showed no morphological changes at embryonic day 16.5 but did have a delay in bone mineralization. Overexpression of a mutant TRPV4 caused a lethal skeletal dysplasia that phenocopied many abnormalities associated with metatropic dysplasia in humans, including dumbbell-shaped long bones, a small ribcage, abnormalities in the autopod, and abnormal ossification in the vertebrae. The difference in phenotype between embryos transgenic for wild-type or mutant Trpv4 demonstrates that an increased amount of wild-type protein can be tolerated and that an activating mutation of this protein is required to produce a skeletal dysplasia phenotype. |
