Scientists have found a mutation in the TMCO3 gene related to short stature in two sisters. The research demonstrated the gene’s role in bone growth and confirmed the mutation’s effects through a mouse model. Conducted at the University Medical Center Hamburg-Eppendorf, the study emphasizes the importance of ion and pH balance in growth.
Through next-generation sequencing, investigators have identified a mutation in the TMCO3 gene in two sisters with short stature. The research, published in the Journal of Bone and Mineral Research, has shed new light on the function of the TMCO3 gene, specifically in the context of bone growth.
Role of TMCO3 in Bone Growth
The research also revealed that the TMCO3 protein is expressed by chondrocytes, cells responsible for bone growth. Furthermore, it has been discovered that TMCO3 regulates the expression of two other proteins known to control bone growth (parathyroid hormone-related protein and Indian hedgehog). TMCO3 appears to transport protons in exchange for potassium across a protein packaging organelle within cells.
Confirmation Through Mouse Model
Scientists confirmed that the mutation in TMCO3 was responsible for the sisters’ short stature by analyzing a mouse model lacking the gene. This analysis showed that the mice had shortened bones, thereby strengthening the link between the gene and this specific growth anomaly.
Collaborative Effort and Implications
“This paper is the result of a great collaboration between the Institute of Human Genetics and the Department of Osteology and Biomechanics, both located at the University Medical Center Hamburg-Eppendorf, in Germany. It shows the importance of ion and pH homeostasis in organismal growth,” said corresponding author Kerstin Kutsche, PhD.
Reference: “TMCO3, a Putative K+:Proton Antiporter at the Golgi Apparatus, Is Important for Longitudinal Growth in Mice and Humans” by Tess Holling, Laura Brylka, Tasja Scholz, Tatjana Bierhals, Theresia Herget, Peter Meinecke, Thorsten Schinke, Ralf Oheim and Kerstin Kutsche, 9 August 2023, Journal of Bone and Mineral Research.