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Diurnal shift of mouse activity by the deficiency of an ageing-related gene Lmna.
Journal of Biochemistry 2022 May 12
Nuclear lamina is a fundamental structure of the cell nucleus and regulates a wide range of molecular pathways. Defects of components of the nuclear lamina cause ageing-like physiological disorders, called laminopathy. Generally, ageing and diseases are often associated with perturbation of various time-of-day-dependent regulations, but it remains elusive whether laminopathy induces any changes of the circadian clock and physiological rhythms. Here, we demonstrated that deficiency of Lmna gene in mice caused an obvious shift of locomotor activities to the daytime. The abnormal activity profile was accompanied by a remarkable change in phase angle between the central clock in the suprachiasmatic nucleus (SCN) and the lung peripheral clocks, leaving the phase of the SCN clock unaffected by the mutation. These observations suggest that Lmna deficiency causes a change of the habitat from nocturnal to diurnal behaviours. On the other hand, molecular oscillation and its phase resetting mechanism were intact in both the Lmna-deficient cells and progeria-mimicking cells. Intriguingly, high-fat diet feeding extended the short lifespan and ameliorated the abnormalities of the behaviours and the phase of the peripheral clock in the Lmna-deficient mice. The present study supports the important contribution of the energy conditions to a shift between the diurnal and nocturnal activities.
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