Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nature genetics [Nat Genet] Journal article

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.

Nature genetics [Nat Genet]

Alleles
Animals
Blotting, Western
Circadian Rhythm
Ethylnitrosourea
Female
Homeostasis
Locomotion
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Point Mutation
Sleep Deprivation
Sleep Disorders
rab3A GTP-Binding Protein