Phenotypes Associated with This Genotype

Genotype
MGI:6189202

• Allelic Composition: Hivep2^tm1Sis/Hivep2^tm1Sis
• Genetic Background: either: (involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj) or (involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj)

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

behavior/neurological

abnormal spatial working memory ( J:263351 )

• 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

anhedonia ( J:263351 )

• 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

abnormal response to social novelty ( J:263351 )

• 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 ( J:263351 )

• 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

increased thermal nociceptive threshold ( J:263351 )

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

abnormal nest building behavior ( J:263351 )

• 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

decreased body weight ( J:263351 )

immune system

CNS inflammation ( J:263351 )

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

nervous system

CNS inflammation ( J:263351 )

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

abnormal dentate gyrus morphology ( J:263351 )

• cell-packing density is higher in the dentate gyrus

abnormal cerebral cortex morphology ( J:263351 )

• reduction in cell density in the prelimbic cortices

• however, no apoptosis or neurodegeneration is seen in the brain

abnormal visual cortex morphology ( J:263351 )

• reduction in cell density in the primary visual cortices

thin cerebral cortex ( J:263351 )

abnormal cerebellar granule cell morphology ( J:263351 )

• 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

decreased oligodendrocyte number ( J:263351 )

• expression of 2,3-cyclic nucleotide 3-phosphodiesterase is decreased, indicating reduced levels of mature oligodendrocytes in the hippocampus

decreased neuron number ( J:263351 )

• parvalbumin+ neuronal number is decreased in the medial prefrontal context and hippocampal CA1 region

abnormal astrocyte physiology ( J:263351 )

• 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

abnormal brain wave pattern ( J:263351 )

• 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

abnormal synaptic transmission ( J:263351 )

• 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

decreased prepulse inhibition ( J:263351 )

• 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