PUBLICATION

Zebrafish Tric-b is required for skeletal development and bone cells differentiation

Authors
Tonelli, F., Leoni, L., Daponte, V., Gioia, R., Cotti, S., Fiedler, I.A.K., Larianova, D., Willaert, A., Coucke, P.J., Villani, S., Busse, B., Besio, R., Rossi, A., Witten, P.E., Forlino, A.
ID
ZDB-PUB-230210-22
Date
2023
Source
Frontiers in endocrinology   14: 10029141002914 (Journal)
Registered Authors
Besio, Roberta, Cotti, Silvia, Coucke, Paul, Daponte, Valentina, Forlino, Antonella, Tonelli, Francesca, Willaert, Andy, Witten, P. Eckhard
Keywords
TRIC-B, bone, collagen, endoplasmic reticulum, fin regeneration, osteogenesis imperfecta, zebrafish
MeSH Terms
  • Bone and Bones/metabolism
  • Animals
  • Zebrafish*/metabolism
  • Calcium/metabolism
  • Osteogenesis Imperfecta*/genetics
  • Cell Differentiation/genetics
  • Ion Channels/genetics
(all 7)
PubMed
36755921 Full text @ Front Endocrinol (Lausanne)
Abstract
Introduction Trimeric intracellular potassium channels TRIC-A and -B are endoplasmic reticulum (ER) integral membrane proteins, involved in the regulation of calcium release mediated by ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors, respectively. While TRIC-A is mainly expressed in excitable cells, TRIC-B is ubiquitously distributed at moderate level. TRIC-B deficiency causes a dysregulation of calcium flux from the ER, which impacts on multiple collagen specific chaperones and modifying enzymatic activity, leading to a rare form of osteogenesis imperfecta (OI Type XIV). The relevance of TRIC-B on cell homeostasis and the molecular mechanism behind the disease are still unknown.
Results In this study, we exploited zebrafish to elucidate the role of TRIC-B in skeletal tissue. We demonstrated, for the first time, that tmem38a and tmem38b genes encoding Tric-a and -b, respectively are expressed at early developmental stages in zebrafish, but only the latter has a maternal expression. Two zebrafish mutants for tmem38b were generated by CRISPR/Cas9, one carrying an out of frame mutation introducing a premature stop codon (tmem38b-/- ) and one with an in frame deletion that removes the highly conserved KEV domain (tmem38bΔ120-7/Δ120-7 ). In both models collagen type I is under-modified and partially intracellularly retained in the endoplasmic reticulum, as described in individuals affected by OI type XIV. Tmem38b-/- showed a mild skeletal phenotype at the late larval and juvenile stages of development whereas tmem38bΔ120-7/Δ120-7 bone outcome was limited to a reduced vertebral length at 21 dpf. A caudal fin regeneration study pointed towards impaired activity of osteoblasts and osteoclasts associated with mineralization impairment.
Discussion Our data support the requirement of Tric-b during early development and for bone cell differentiation.
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Citation
Tonelli, F., Leoni, L., Daponte, V., Gioia, R., Cotti, S., Fiedler, I.A.K., Larianova, D., Willaert, A., Coucke, P.J., Villani, S., Busse, B., Besio, R., Rossi, A., Witten, P.E., Forlino, A. (2023) Zebrafish Tric-b is required for skeletal development and bone cells differentiation. Frontiers in endocrinology. 14:10029141002914.