Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV4

Title: Mice expressing mutant Trpv4 recapitulate the human TRPV4 disorders.

Authors: Michael M Weinstein, Stuart W Tompson, Yuqing Chen, Brendan Lee, Daniel H Cohn

Journal, date & volume: J. Bone Miner. Res., 2014 Aug , 29, 1815-22

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24644033

Abstract
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.