Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse.
Rab3a is the most abundant Rab ( ras-associated binding) protein in the brain and has a regulatory role in synaptic vesicle trafficking. Mice with a targeted loss-of-function mutation in Rab3a have defects in Ca(2+)-dependent synaptic transmission: the number of vesicles released in response to an action potential is greater than in wildtype mice, resulting in greater synaptic depression and the abolishment of CA3 mossy-fiber long term potentiation. The effect of these changes on behavior is unknown. In a screen for mouse mutants with abnormal rest-activity and sleep patterns, we identified a semidominant mutation, called earlybird, that shortens the circadian period of locomotor activity. Sequence analysis of Rab3a identified a point mutation in the conserved amino acid (Asp77Gly) within the GTP-binding domain of this protein in earlybird mutants, resulting in significantly reduced levels of Rab3a protein. Phenotypic assessment of earlybird mice and a null allele of Rab3a revealed anomalies in circadian period and sleep homeostasis, providing evidence that Rab3a-mediated synaptic transmission is involved in these behaviors.[1]References
- Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Kapfhamer, D., Valladares, O., Sun, Y., Nolan, P.M., Rux, J.J., Arnold, S.E., Veasey, S.C., Bućan, M. Nat. Genet. (2002) [Pubmed]
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