Phenotypes Associated with This Genotype

Genotype
MGI:6189158

• Allelic Composition: Camk2a^tm1Sva/Camk2a⁺
• Genetic Background: B6.129P2-Camk2a^tm1Sva/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

impaired spatial working memory ( J:263327 )

• severe working memory deficits in the eight-arm radial maze task and delayed alternation task using modified T-maze

• however, performance in reference memory tasks are normal

increased aggression towards mice ( J:263327 )

• mice exhibit high levels of aggression towards cage mates, with more than half of cage mates killed by mutants by 3 years of age

• however, mice exhibit normal body temperature and normal behaviors in the wire hang test, grip strength test, rotarod test, hot plate test, acoustic startle response, and prepulse inhibition test

decreased depression-related behavior ( J:263327 )

• depression-like behavior is decreased in the Porsolt forced swim test

decreased anxiety-related response ( J:263327 )

• anxiety-like behavior is decreased both in the light/dark transition test and in the elevated plus maze test

abnormal locomotor behavior ( J:234969 , J:263327 )

• mice exhibit exaggerated infradian oscillatory locomotor activity, with 24 hour locomotor activity positively correlated with time spent in the center of the open field, negatively correlated with percentage of immobility time in the force swim test, and correlated with anxiety- and depression-like behaviors (J:234969)

• expression of many circadian genes correlates with infradian rhythm behavior (J:234969)

• infradian oscillatory locomotor activity responds to mood stabilizer treatment, with lamotrigine increasing home cage locomotor activity and carbamazepine decreasing home cage locomotor activity (J:234969)

• mice exhibit an exaggerated infradian rhythm (J:263327)

• pattern of locomotor activity changes over time, showing periodic mood-change-like behavior in the home cage, with one cycle of approximately 1-2 weeks (J:263327)

• mice show more variable activity patterns in the total distance traveled in the dark period in their home cages (J:263327)

• the locomotor activity pattern during a single day is different, with activity steadily increasing until morning compared to wild-type mice which have two peaks of activity during the dark phase (J:263327)

increased locomotor activity ( J:263327 )

• mice show increased locomotor activity in the open field and in the social interaction test in a novel environment

growth/size/body

decreased body weight ( J:263327 )

cellular

increased cell proliferation ( J:263327 )

• BrdU-labeled cells are increased by 53% in the dentate gyrus, indicating increased proliferation in this region

nervous system

abnormal dentate gyrus morphology ( J:263327 )

• mice exhibit increased number of immature neurons and decreased number of mature neurons in the dentate gyrus, decreased dendritic branching and length in the dentate gyrus, and neurons with electrophysiological features characteristic of immature neurons, indicating that the dentate gyrus is immature

abnormal hippocampus granule cell morphology ( J:263327 )

• majority of dentate gyrus granule cells fail to develop into mature neurons

abnormal synapse morphology ( J:263327 )

• the mossy fiber-CA3 synapses are poorly developed in the hippocampus

abnormal postsynaptic density morphology ( J:263327 )

• formation of postsynaptic densities in the mossy fiber terminals is reduced

abnormal synaptic vesicle morphology ( J:263327 )

• formation of synaptic vesicles in the mossy fiber terminals is reduced

abnormal neuron physiology ( J:263327 )

• dentate gyrus neurons exhibit functional abnormalities, including higher input resistance, slightly depolarized resting membrane potentials, high excitability, decreased number of spikes during sustained depolarization, and greatly reduced facilitation at mossy fiber-CA3 synapses

abnormal CNS synaptic transmission ( J:263327 )

• mutants show abnormal transmission at the synapses between granule cell axons, mossy fibers, and the CA1 pyramidal cells, with increased basal transmission and decreased large facilitation

• increase in striatal dopamine turnover in the brain

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
bipolar disorder		DOID:3312		J:234969