Details

Autor(en) / Beteiligte

• Schwerd, Tobias
• Krause, Freia
• Twigg, Stephen R F
• Aschenbrenner, Dominik
• Chen, Yin-Huai
• Borgmeyer, Uwe
• Müller, Miryam
• Manrique, Santiago
• Schumacher, Neele
• Wall, Steven A
• Jung, Jonathan
• Damm, Timo
• Glüer, Claus-Christian
• Scheller, Jürgen
• Rose-John, Stefan
• Jones, E Yvonne
• Laurence, Arian
• Wilkie, Andrew O M
• Schmidt-Arras, Dirk
• Uhlig, Holm H

Titel

A variant in IL6ST with a selective IL-11 signaling defect in human and mouse

Ist Teil von

• Bone research, 2020-06, Vol.8 (1), p.24-24

Ort / Verlag

China: Springer Nature B.V

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The GP130 cytokine receptor subunit encoded by is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in (p.R281Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant p.R279Q. We show that human GP130 p.R281Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice p.R279Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.