We have located links that may give you full text access.
Defective joint development and maintenance in GDF6-related multiple synostoses syndrome.
Journal of Bone and Mineral Research 2023 Februrary 7
Multiple synostoses syndromes (SYNS) are a group of rare genetic bone disorders characterized by multiple joint fusions. We previously reported an SYNS4-causing GDF6 c.1330T>A (p.Tyr444Asn) mutation, which reduced Noggin-induced GDF6 inhibition and enhanced SMAD1/5/8 signaling. However, the mechanisms by which GDF6 gain-of-function mutation alters joint formation and the comprehensive molecular portraits of SYNS4 remain unclear. Herein, we introduced the p.Tyr443Asn (orthologous to the human GDF6 p.Tyr444Asn) mutation into the mouse Gdf6 locus and performed extensive phenotype analysis, joint development investigation, and transcriptome profiling of Gdf6 p.Tyr443Asn limb buds. Gdf6 p.Tyr443Asn knock-in mice recapitulated the morphological features of human SYNS4, showing joint fusion in the wrists, ankles, phalanges, and auditory ossicles. Analysis of mouse embryonic forelimbs demonstrated joint interzone formation defects and excess chondrogenesis in Gdf6 p.Tyr443Asn knock-in mice. Further RNA sequencing of forelimb buds revealed enhanced bone formation and upregulated bone morphogenetic protein (BMP) signaling in mice carrying the Gdf6 p.Tyr443Asn mutation. As tightly regulated BMP signaling is critical for skeletal development and joint morphogenesis, our study shows that enhancing GDF6 activity has a significant impact in both prenatal joint development and postnatal joint maintenance. This article is protected by copyright. All rights reserved.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app