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bioRxiv · 10.1101/2025.01.19.633799

The Role Of Fzd8 For Bone Development And Homeostasis In A Mouse Model Generated By CRISPR/Cas9 Genome Editing

Lin, Z.·He, J.·Huang, H.·Lin, X.·Chen, H.·Zhang, W.·Chen, J.
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Abstract

BackgroundFZD8 could be a promising therapeutic target in osteoporosis (OP), although the signal transduction mechanism in OP regarding FZD8 has not been completely elucidated. AimsWe used the CRISPR/Cas9 technique to develop an Fzd8-knockout mouse model to study whether Fzd8 inactivation results in genetic changes with potential correlations to OP. Materials and MethodsGenotypes of distinguished classified knockout mice, i.e., heterozygous, homozygous, and wild-type were identified through PCR. Applying the murine model, third generation mice were used for the downstream experiments. We investigated the potential relevance of differentially expressed genes (DEGs) in OP. ResultsWe found that osteoclasts significantly increased in Fzd8-knockout homozygous mice, compared to wild-type mice, while osteoblasts reduced significantly. Before transcription, heterozygous and homozygous mice possessed DEGs related to exons SNP, which are associated with exons CNV. After transcription, DEGs related to exons SNP in heterozygous and homozygous mice were observed, some of which are potentially associated with OP based on pathway and gene set enrichment analyses. ConclusionsOur Fzd8-knockout murine model showed that there were significant alternations in Fzd10 and Lta gene expressions and Itgb3 and RANK protein expressions among the wild-type and homozygous mice, which are significantly associated with bone remodeling. Our results revealed that FZD8 could be a therapeutic target in OP. This study elucidates the molecular mechanisms in OP, providing evidence-based data for OP drug development and treatment.

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Lin, Z., He, J., Huang, H., Lin, X., Chen, H., Zhang, W., Chen, J.. 2025-01-19. The Role Of Fzd8 For Bone Development And Homeostasis In A Mouse Model Generated By CRISPR/Cas9 Genome Editing. https://doi.org/10.1101/2025.01.19.633799

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