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The Progress of CRISPR/Cas9-Mediated Gene Editing in Generating Mouse/Zebrafish Models of Human Skeletal Diseases
Nan Wu1,2,3, Bowen Liu1,2, Huakang Du1,2
1Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Abstract:
Genetic factors play a substantial role in the etiology of skeletal diseases, which involve 1) defects in skeletal development, including intramembranous ossification and endochondral ossification; 2) defects in skeletal metabolism, including late bone growth and bone remodeling; 3) defects in early developmental processes related to skeletal diseases, such as neural crest cell (NCC) and cilia functions; 4) disturbance of the cellular signaling pathways which potentially affect bone growth. Efficient and high-throughput genetic methods have enabled the exploration and verification of disease-causing genes and variants. Animal models including mouse and zebrafish have been extensively used in functional mechanism studies of causal genes and variants. The conventional approaches of generating mutant animal models include spontaneous mutagenesis, random integration, and targeted integration via mouse embryonic stem cells. These approaches are costly and time-consuming. Recent development and application of gene-editing tools, especially the CRISPR/Cas9 system, has significantly accelerated the process of gene-editing in diverse organisms. Here we review both mice and zebrafish models of human skeletal diseases generated by CRISPR/Cas9 system, and their contributions to deciphering the underpins of disease mechanisms.
Insights
Genetic factors significantly impact skeletal diseases affecting development and metabolism. The CRISPR/Cas9 system accelerates the creation of mouse and zebrafish models for studying these genetic causes.
Area of Science:
- Genetics
- Developmental Biology
- Orthopedics
Background:
- Skeletal diseases stem from genetic factors impacting bone development, metabolism, and cellular processes.
- Traditional methods for creating genetic animal models are time-consuming and expensive.
- Advancements in gene-editing technologies, particularly CRISPR/Cas9, offer faster and more efficient model generation.
Purpose of the Study:
- To review the application of CRISPR/Cas9 in generating mouse and zebrafish models for human skeletal diseases.
- To highlight the contribution of these models in understanding disease mechanisms.
Main Methods:
- Review of literature on CRISPR/Cas9-generated mouse and zebrafish models.
- Analysis of studies investigating genetic factors in skeletal development and metabolism.
Main Results:
- CRISPR/Cas9 has significantly accelerated the creation of genetically modified mouse and zebrafish models.
- These models are crucial for functional studies of genes and variants implicated in skeletal diseases.
- The review covers models for various skeletal defects, including ossification, growth, and signaling pathway disturbances.
Conclusions:
- CRISPR/Cas9 technology is revolutionizing the study of genetic skeletal diseases.
- Mouse and zebrafish models generated via CRISPR/Cas9 are invaluable tools for deciphering disease underpinnings.
- This approach facilitates a deeper understanding of skeletal development, metabolism, and related disorders.
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