Zebrafish Skeletal Disease Models

Zebrafish Skeletal Disease Models

In recent years, Danio rerio (zebrafish) has become widely used as small animal model for human diseases. This is because of the unique characteristics of the embryo such as small size, rapid external development, and transparency of the larval body. These advantages encourage the use of live imaging and powerful genetic tools based on mutagenesis. Besides, automated systems have been coupled with zebrafish embryo to create one of the most important in vivo methods for drug discovery, drug screening, and toxicity testing.

As vertebrates, the zebrafish and mammalian skeletons are very similar. Although mechanics of the mammalian (terrestrial) and fish (aquatic) skeletons differ owing to their habitats, their similarities are strongest at the level of basic cellular functions of osteocytes and chondrocytes and their primary role of secreting extracellular matrix (ECM). The similarity of the adult skeletal structure between Danio rerio and Homo sapiens has hired zebrafish as an animal model to study multiple aspects of skeletal physiology and pathology: bone metabolism, resorbing activity, and tissue turnover. Within the transparent body of zebrafish, morphogenetic processes and physiological activities of the skeleton are easily accessible, and the osteocytes and chondrocytes can be labeled with simple stains, allowing for rapid and high-throughput assessment of the skeleton.

Zebrafish models have been generated for many genes associated with human genetic disorders that affect the skeleton. These human disorders include craniosynostoses, osteogenesis imperfecta (OI), as well as general dysplasias. Genes affecting mineral metabolism include transcription factors, collagen-associated genes and signaling molecules, matrix proteins.

Table 1. Selection of genetic models in zebrafish for human genes associated with bone mineral density (BMD) GWAS

Human GeneHuman GWAS or Disease/TraitZebrafish Phenotype (age)
COL11A1Stickler/Marshall syndrome; Estimated BMDAbnormally thick and sparse fibrils in the cartilage extracellular matrix/perichordal sheath
CYP26Coronal craniosynostosis; Estimated BMDFusions of the vertebral centra, cartilaginous outgrowths of the endochondral fin elements (dolphin; larvae); Coronal Craniosynostosis (stocksteif; juvenile)
ENPP1hypermineralization of the axial skeleton; BMDPatchy mineralization of craniofacial bones; ectopic calcifications; overexpress spp1 (Osteopontin; 6–9 dpf); fusion in vertebral bodies, neural and haemal arches (juvenile)
JAG1Alagille syndrome; BMDFacial defects; dorsal hyoid and mandibular arch fusion (5 dpf)
LRP5Osteoporosis-pseudoglioma (OPPG), craniosynostosis; BMDSevere defects in the ventral craniofacial skeleton (7 dpf)
MEF2CAuriculocondylar syndrome; BMDMalformed faces; ventrally displaced jaws. Ectopic cartilage; dorsal/ventral joints missing; enlarged ventral hyoid bone (5 dpf)
RUNX2Cleidocranial dysplasia; Estimated BMDMorphants displayed no overt abnormalities (3.5-5dpf)
SPP1BMDReduction in the formation of endochondral and dermal bone (5–15 dpf)
SOX9Campomelic dysplasia; BMDCurly-down body axis (4–5 dpf); actinotrichia missing (double mutant)
TGFB2Estimated BMDShortening and misshaping of the jaw, parasphenoid, and ethmoid plate

Our Zebrafish Skeletal Disease Models

Creative Biogene has long-standing experience in conducting preclinical zebrafish model studies of skeletal disease. We can offer multiple routes of gene depletion strategies to generate the zebrafish model, including classical chemical mutagenesis, insertional mutagenesis, gene knockdown by morpholino oligonucleotide (MO) injections, and CRISPR/Cas9 genome editing systems. Many pathological models have been established in adult zebrafish at Creative Biogene, such as bone injury models, osteogenesis imperfecta models, osteoporosis models, arterial calcification models, and osteoarthritis models. These zebrafish models have shown high correspondence of clinical output with human patients affected by skeletal diseases.


  • Easily monitoring the development and function of the heart and vasculature
  • Transgenic models available
  • Large-scale mutagenesis
  • High-throughput genetic/drug screening

Creative Biogene has the expertise and experience to assist you in assessing the therapeutic potential of your compounds for the skeletal disease. Contact us today to discuss your objectives and how we can reach them.


  • Kwon R Y, et al. Using zebrafish to study skeletal genomics. Bone, 2019, 126: 37-50.
  • Lleras-Forero L, et al. Zebrafish and medaka as models for biomedical research of bone diseases. Developmental biology, 2020, 457(2): 191-205.
  • Luderman L N, et al. Zebrafish developmental models of skeletal diseases. Current topics in developmental biology. Academic Press, 2017, 124: 81-124.
  • Carnovali M, et al. Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together. BioMed Research International, 2019, 2019.

For research use only. Not intended for any clinical use.

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