PUBLICATION
Genetic ablation of Pth4 disrupts calcium-phosphate balance, bone development, and kidney transcriptome in teleosts
- Authors
- Méndez-Martínez, L., Suarez-Bregua, P., Guerrero-Peña, L., Barreiro-Docío, E., Costas-Prado, C., Cobelo-García, A., Rotllant, J.
- ID
- ZDB-PUB-250829-7
- Date
- 2025
- Source
- General and comparative endocrinology : 114805114805 (Journal)
- Registered Authors
- Rotllant, Josep
- Keywords
- Bone, CRISPR, Calcium, Fish, Kidney, Phosphate, Pth4
- MeSH Terms
-
- Homeostasis/genetics
- Zebrafish/genetics
- Zebrafish/metabolism
- Phosphates*/metabolism
- Animals
- Parathyroid Hormone*/genetics
- Parathyroid Hormone*/metabolism
- Bone Development*/genetics
- Bone Development*/physiology
- Transcriptome*/genetics
- Calcium*/metabolism
- Kidney*/metabolism
- PubMed
- 40876765 Full text @ Gen. Comp. Endocrinol.
Citation
Méndez-Martínez, L., Suarez-Bregua, P., Guerrero-Peña, L., Barreiro-Docío, E., Costas-Prado, C., Cobelo-García, A., Rotllant, J. (2025) Genetic ablation of Pth4 disrupts calcium-phosphate balance, bone development, and kidney transcriptome in teleosts. General and comparative endocrinology. :114805114805.
Abstract
Parathyroid hormone 4 (Pth4) is an evolutionarily conserved member of the PTH family, expressed in hypothalamic neurons and lost in eutherian mammals. In order to elucidate its role in mineral homeostasis and skeletal development, a pth4 knockout (pth4KO) zebrafish line was generated using CRISPR/Cas9 and transcriptomic profiling was conducted across six key tissues: brain, kidney, intestine, gills, scales, and bone. The results obtained demonstrated that the loss of Pth4 led to pronounced disturbances in calcium and phosphate homeostasis, skeletal deformities, and widespread tissue-specific transcriptional alterations. Notably, dysregulation of mineral regulatory genes-such asfgf23,phex, andslc34a1a was particularly evident in the kidney, suggesting disruption of the FGF23-Klotho axis. In parallel, differential expression of extracellular matrix genes (col1a1a,col10a1a,col11a1) and matrix remodeling enzymes (mmp9,mmp13a,mmp2) in bone and scales indicated impaired skeletal remodeling. Together, these findings highlight a pivotal role for Pth4 in the endocrine and local regulation of mineral metabolism and skeletal integrity, expanding our understanding of PTH family functions in vertebrate physiology.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping