Functional Validation of Osteoporosis Genetic Findings Using Small Fish Models

Erika Kague, David Karasik

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


The advancement of human genomics has revolutionized our understanding of the genetic architecture of many skeletal diseases, including osteoporosis. However, interpreting results from human association studies remains a challenge, since index variants often reside in non-coding regions of the genome and do not possess an obvious regulatory function. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary, such as the one offered by animal models. These models enable us to identify causal mechanisms, clarify the underlying biology, and apply interventions. Over the past several decades, small teleost fishes, mostly zebrafish and medaka, have emerged as powerful systems for modeling the genetics of human diseases. Due to their amenability to genetic intervention and the highly conserved genetic and physiological features, fish have become indispensable for skeletal genomic studies. The goal of this review is to summarize the evidence supporting the utility of Zebrafish (Danio rerio) for accelerating our understanding of human skeletal genomics and outlining the remaining gaps in knowledge. We provide an overview of zebrafish skeletal morphophysiology and gene homology, shedding light on the advantages of human skeletal genomic exploration and validation. Knowledge of the biology underlying osteoporosis through animal models will lead to the translation into new, better and more effective therapeutic approaches.

Original languageEnglish
Article number279
Issue number2
StatePublished - Feb 2022

Bibliographical note

Funding Information:
The authors acknowledge the COST Action GEMSTONE consortium, supported by COST (European Cooperation in Science and Technology CA18139). DK was supported by ISF grant #1121/19. EK was supported by Versus Arthritis, grant #21937.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Causal gene
  • Data integration
  • Gene regulation
  • Genome-wide association study
  • Osteoblast
  • Osteoclast
  • Skeletal disease
  • Zebrafish


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