| First Author | Kapfhamer D | Year | 2002 |
| Journal | Nat Genet | Volume | 32 |
| Issue | 2 | Pages | 290-5 |
| PubMed ID | 12244319 | Mgi Jnum | J:79562 |
| Mgi Id | MGI:2388496 | Doi | 10.1038/ng991 |
| Citation | Kapfhamer D, et al. (2002) Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nat Genet 32(2):290-5 |
| abstractText | 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<sup>2+</sup>-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. |
