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Decrease in phosphatidylserine synthesis in brain microsomes of Shambling mutant mouse.

T Yamaguchi, Y Matsumura, M Yamaguchi

    Biochemistry International
    |March 1, 1984
    PubMed
    Summary
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    Shambling mutant mice show reduced phosphatidylserine (PS) synthesis in the brain. This defect is linked to calmodulin-dependent synthesis and can be partially corrected by thyrotropin-releasing hormone (TRH).

    Area of Science:

    • Neurochemistry
    • Biochemistry
    • Genetics

    Background:

    • Phosphatidylserine (PS) is crucial for neuronal function and membrane integrity.
    • The Shambling mutant mouse exhibits ataxia, suggesting neurological dysfunction.
    • Calmodulin plays a role in regulating various cellular processes, including lipid synthesis.

    Purpose of the Study:

    • To investigate the rate of phosphatidylserine (PS) synthesis in the brain microsomes of ataxic and heterozygous Shambling mutant mice.
    • To determine the role of calmodulin in the observed decrease in PS synthesis.
    • To explore the potential of thyrotropin-releasing hormone (TRH) in modulating PS synthesis and compensating for the genetic defect.

    Main Methods:

    • Measurement of phosphatidylserine (PS) synthesis rates in brain microsomes from control and Shambling mutant mice.

    Related Experiment Videos

  • Assay of PS synthesis in the presence of varying calmodulin concentrations.
  • In vitro assessment of TRH's effect on PS synthesis rates.
  • Main Results:

    • Ataxic Shambling mutant mice displayed a 40% reduction in brain PS synthesis compared to controls.
    • Heterozygous nonataxic mutants showed an 80% rate of PS synthesis.
    • The reduction in PS synthesis in ataxic mutants correlated with calmodulin-sensitive PS synthesis in control brains.
    • Thyrotropin-releasing hormone (TRH) significantly enhanced PS synthesis rates in vitro, compensating for the genetic defect.

    Conclusions:

    • The genetic defect in Shambling mutant mice leads to a significant reduction in brain phosphatidylserine (PS) synthesis.
    • Calmodulin-dependent pathways are implicated in the PS synthesis deficit.
    • Thyrotropin-releasing hormone (TRH) shows potential as a therapeutic agent to restore PS synthesis and potentially ameliorate motor deficits.