Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background.
Sandy mice have a deletion mutation in the gene encoding dysbindin-1, Dtnbp1, with consequent reduction of the protein in heterozygotes and its loss in homozygotes. The sandy mouse thus serves as an animal model of dysbindin-1 function. As this protein is concentrated in synaptic tissue and affects transmitter release, it may affect neuronal processes that mediate behavior. To investigate the neurobehavioral effects of the Dtnbp1 mutation, we studied littermate sandy and wild-type controls on a C57BL/6J genetic background. The three animal groups were indistinguishable in their external physical characteristics, sensorimotor skills and indices of anxiety-like behaviors. In the open field, however, homozygous animals were hyperactive and appeared to show less habituation to the initially novel environment. In the Morris water maze, homozygous animals displayed clear deficits in spatial learning and memory with marginal deficits in visual association learning. Apart from the last mentioned deficits, these abnormalities are consistent with hippocampal dysfunction and in some cases with elevated dopaminergic transmission via D2 dopamine receptors. As similar deficits in spatial learning and memory have been found in schizophrenia, where decreased dysbindin-1 has been found in the hippocampus, the sandy mouse may also model certain aspects of cognition and behavior relevant to schizophrenia.
Cox
M M
MM
Center for Neurobiology & Behavior, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tucker
A M
AM
Tang
J
J
Talbot
K
K
Richer
D C
DC
Yeh
L
L
Arnold
S E
SE
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005106:Exploratory Behavior / Q000502:physiology; D005838:Genotype; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009154:Mutation / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D009498:Neurotoxins / Q000633:toxicity; D004856:Postural Balance / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D009498:Neurotoxins