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; Glueer, Claus-Christian; Scheller, Jürgen; Rose-John, Stefan; Jones, E. Yvonne; Laurence, Arian; Wilkie, Andrew O. M.; Schmidt-Arras, Dirk; Uhlig, Holm H. (2020): A variant in IL6ST with a selective IL-11 signaling defect in human and mouse. In: Bone Research, Vol. 8, No. 1, 24 |
Abstract
The GP130 cytokine receptor subunit encoded byIL6STis the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant inIL6ST(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 variantIl6stp.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 miceIl6stp.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 ofIL11RAdeficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 2095-4700 |
Language: | English |
ID Code: | 86042 |
Deposited On: | 25. Jan 2022 09:17 |
Last Modified: | 25. Jan 2022 09:17 |
- BASE
- 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
- Glueer, Claus-Christian
- Scheller, Jürgen
- Rose-John, Stefan
- Jones, E. Yvonne
- Laurence, Arian
- Wilkie, Andrew O. M.
- Schmidt-Arras, Dirk
- Uhlig, Holm H.
- Google Scholar
- 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
- Glueer, Claus-Christian
- Scheller, Jürgen
- Rose-John, Stefan
- Jones, E. Yvonne
- Laurence, Arian
- Wilkie, Andrew O. M.
- Schmidt-Arras, Dirk
- Uhlig, Holm H.