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Hyperactivity, Memory Defects, and Craniofacial Abnormalities in Zebrafish fmr1 Mutant Larvae

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Abstract

Fragile X syndrome (FXS) is a heritable mental retardation disease caused by unstable trinucleotide repeat sequences in FMR1. FXS is characterized by delayed development, hyperactivity, and autism behavior. Zebrafish is an excellent model to study FXS and the underlying function of fmr1. However, at present, fmr1 function is mainly studied via morpholinos or generated mutants using targeting induced local lesions in genomes. However, both of these methods generate off-target effects, making them suboptimal techniques for studying FXS. In this study, CRISPR/Cas9 technology was used to generate two zebrafish fmr1 mutant lines. High-throughput behavior analysis, qRT-PCR, and alcian blue staining experiments were employed to investigate fmr1 function. The fmr1 mutant line showed abnormal behavior, learning memory defects, and impaired craniofacial cartilage development. These features are similar to the human FXS phenotype, indicating that the fmr1 mutant generated in this study can be used as a new model for studying the molecular pathology of FXS. It also provides a suitable model for high-throughput screening of small molecule drugs for FXS therapeutics.

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Acknowledgements

This work was supported by grants from the Industry-University Collaboration Project of Jiangsu Province (BY2016049-02), National Natural Science Foundation of China (21876198), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions and Research Foundation of the Affiliated Children's Hospital of Xi'an Jiaotong University (2018A04).

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Author notes

  1. Jia Hu and Lei Chen have contributed equally.

Authors and Affiliations

  1. School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou, 215123, Jiangsu, People’s Republic of China

    Jia Hu

  2. Department of Medical Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, People’s Republic of China

    Lei Chen

  3. CAS Key Lab of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, Jiangsu, People’s Republic of China

    Jian Yin, Huancai Yin & Jingjing Tian

  4. Shaanxi Institute of Pediatric Diseases, Xi’an Children’s Hospital, Xi’an, 710003, Shaanxi, People’s Republic of China

    Yinong Huang

  5. Academy for Engineering & Technology, Fudan University, Shanghai, 200433, People’s Republic of China

    Jingjing Tian

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  1. Jia Hu
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  2. Lei Chen
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  3. Jian Yin
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  4. Huancai Yin
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Correspondence to Yinong Huang or Jingjing Tian.

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Conflict of interest

Jia Hu, Lei Chen, Jian Yin, Huancai Yin, Yinong Huang, and Jingjing Tian declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures were approved by the Fudan University Animal Care and Use Committee and were performed in accordance with the governmental regulations of China.

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Hu, J., Chen, L., Yin, J. et al. Hyperactivity, Memory Defects, and Craniofacial Abnormalities in Zebrafish fmr1 Mutant Larvae. Behav Genet 50, 152–160 (2020). https://doi.org/10.1007/s10519-020-09995-7

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  • DOI: https://doi.org/10.1007/s10519-020-09995-7

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