| Title | Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. | | Author(s) | Kapfhamer D, Valladares O, Sun Y, Nolan PM, Rux JJ, Arnold SE, Veasey SC, Bućan M | | Institution | Center for Neurobiology of Behavior of the Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. | | Source | Nat Genet 2002 Oct; 32(2):290-5. | | MeSH | 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
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, U.S. Gov't, P.H.S.
| | PubMed ID | 12244319 |
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