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Phenotypes Associated with This Genotype
Genotype
MGI:6189202
Allelic
Composition
Hivep2tm1Sis/Hivep2tm1Sis
Genetic
Background
either: (involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj) or (involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hivep2tm1Sis mutation (2 available); any Hivep2 mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mice exhibit severe working memory deficits in the eight-arm radial maze and T-maze forced-alternation task
• in reversal learning, mutants perform better than controls
• however, performance in the T-maze left-right discrimination task is normal
• mice treated with rolipram and ibuprofen, anti-inflammatory drugs, show improved working memory in the T-maze
• depression-like behavior is increased in sucrose preference test
• however, treatment with the anti-inflammatory drugs rolipram and ibuprofen has no effect on the anhedonia in the sucrose preference test
• mice show impaired sociability and novelty preference in Crawleys sociability and social novelty preference test
• mice show decreased social interaction in the conventional social interaction test in a novel environment
• hyperactivity in the open field test and in home cages
• treatment with the antipsychotic haloperidol or clozapine decreases hyperactivity
• MK801, an NMDA antagonist, treatment produces a higher level of drug-stimulated motor activation in mutants than in controls
• in the Porsolt forced swim test, mice show reduced immobility, possibly due to hyperactivity
• treatment with the anti-inflammatory drugs rolipram and ibuprofen has no effect on locomotor activity
• mice exhibit decreased sensitivity to pain in the hot plate test
• mice show severely impaired nestlet shredding and nest building, with nestlets being left intact by about 80% of mutants
• mice treated with rolipram and ibuprofen, anti-inflammatory drugs, show improved nest-building behavior

growth/size/body

immune system
• analysis of the changes in gene expression indicates chronic CNS inflammation

integument
• mice exhibit decreased sensitivity to pain in the hot plate test

nervous system
• analysis of the changes in gene expression indicates chronic CNS inflammation
• cell-packing density is higher in the dentate gyrus
• reduction in cell density in the prelimbic cortices
• however, no apoptosis or neurodegeneration is seen in the brain
• reduction in cell density in the primary visual cortices
• mice show increased expression of immature-neuronal markers and decreased expression of mature granule cell markers, indicating an increase of immature neurons and decreased mature neurons, and dentate gyrus granule cell maturation defects
• granule cells show somatic electrophysiological features similar to those of immature granule cells, with high input resistance, lower current threshold for firing, a short latency to the first spike, a deceased number of spikes during sustained depolarization in response to current injection
• granule cells in the dentate gyrus show decreased cell membrane capacitance, indicating a smaller cell surface area
• expression of 2,3-cyclic nucleotide 3-phosphodiesterase is decreased, indicating reduced levels of mature oligodendrocytes in the hippocampus
• parvalbumin+ neuronal number is decreased in the medial prefrontal context and hippocampal CA1 region
• astrocytes, but not microglias, are activated indicating inflammation within the 45hippocampus
• mice treated with rolipram and ibuprofen, anti-inflammatory drugs, show a reduction in the number of activated astrocytes in the hippocampus but not in the prefrontal cortex
• cortical EEG in freely moving mites show an increase of power in the theta band and decrease in the gamma band, indicating increased low-frequency and decreased high-frequency energy in the cortex
• the ratio of peak mossy fiber excitatory postsynaptic potential (EPSP) amplitude to fiber volley amplitude is increased, indicating augmentation of basal synaptic transmission
• strong frequency facilitation is greatly decreased at the mossy fiber synapse
• prepulse inhibition of the acoustic startle response is reduced
• however, the amplitude of the acoustic startle response is similar to wild-type mice
• administration of a high-dose of haloperiodol, an antipsychotic, improves the prepulse inhibition impairment
• however, treatment with the anti-inflammatory drugs rolipram and ibuprofen has no effect on the impaired pre-pulse inhibition during the startle response

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
schizophrenia DOID:5419 OMIM:181500
J:263351


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
03/13/2019
MGI 6.13
The Jackson Laboratory