Knockout SOD1 in rats leads to amyotrophic lateral sclerosis (ALS)
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Institute of laboratory animal sciences, CAMS

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CAMS Innovation Fund for Medical Sciences (2021-I2M-1-024, and 2023-I2M-2-001), State Key Laboratory Special Fund (2060204), Fundamental Research Funds for the Central Universities (3332022040 and 3332023164), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2023-PT180-01), and Haihe Laboratory of Cell Ecosystem Innovation Fund (HH24KYZX0007).

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    Abstract:

    Objective To establish Sod1 knockout rats and analyze its neurological disease phenotypes. Methods Sod1 knockout rats were generated using CRISPR/Cas9 technology. Genotyping was performed via PCR and Sanger sequencing. Protein expression was validated by Western blot. Knockout rats were crossed with wild-type rats to assess stable inheritance through generations. Phenotypic analyses included: monitoring body weight and survival curves, histopathological examination, behavioral test, analyze the motor neuron changes and status of neuroinflammation. Results? Genotypic analyzation demonstrated successful establishment of Sod1 knockout rats. Altered morphology and reduced body weight indicated impaired development in knockout rats. Behavioral tests revealed impaired motor function, exhibiting ALS-like phenotypes. Pathological findings included: reduced L4 motor neurons in the lumbar spinal cord; significant microglial infiltration; decreased cell number and cross-sectional area in gastrocnemius muscle. Conclusion? We successfully established Sod1 knockout rats exhibiting key ALS pathological features. This model provides a valuable platform for investigating SOD1"s role in ALS pathogenesis and mechanistic studies.

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History
  • Received:August 13,2025
  • Revised:August 29,2025
  • Adopted:November 05,2025
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