Phenotypes associated with this allele

• Allele Symbol: Hivep2^tm1Sis
• Allele Name: targeted mutation 1, Shunsuke Ishii
• Allele ID: MGI:2182914
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hivep2^tm1Sis/Hivep2^tm1Sis	C.Cg-Hivep2^tm1Sis	MGI:3615668
hm2	Hivep2^tm1Sis/Hivep2^tm1Sis	either: (involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj) or (involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj)	MGI:6189202
hm3	Hivep2^tm1Sis/Hivep2^tm1Sis	involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj	MGI:3615664
hm4	Hivep2^tm1Sis/Hivep2^tm1Sis	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:6189180
ht5	Hivep2^tm1Sis/Hivep2^+	involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj	MGI:3615665
cx6	Hivep2^tm1Sis/Hivep2^tm1Sis Tg(DO11.10)10Dlo/?	involves: BALB/cA * C3H * C57BL/6NCrlj * CBA/JNCrlj	MGI:3615666

Genotype
MGI:3615668

hm1

• Allelic Composition: Hivep2^tm1Sis/Hivep2^tm1Sis
• Genetic Background: C.Cg-Hivep2^tm1Sis

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

immune system

abnormal T-helper 2 cell morphology ( J:96024 )

• enhanced generation of TH2 cells

• slightly enhanced cell division rate of CD4+ cells under conditions that enhance TH2 generation

hematopoietic system

abnormal T-helper 2 cell morphology ( J:96024 )

• enhanced generation of TH2 cells

• slightly enhanced cell division rate of CD4+ cells under conditions that enhance TH2 generation

Genotype
MGI:6189202

hm2

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

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

Genotype
MGI:3615664

hm3

• Allelic Composition: Hivep2^tm1Sis/Hivep2^tm1Sis
• Genetic Background: involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj

immune system

abnormal thymus lobule morphology ( J:72249 )

abnormal thymus cortex morphology ( J:72249 )

• greatly expanded cortex area containing double positive cells

enlarged thymus cortex ( J:72249 )

• grossly expanded

abnormal thymus medulla morphology ( J:72249 )

• rudimentary medulla where single positive cells are located

abnormal immune system cell morphology ( J:72249 )

decreased single-positive T cell number ( J:72249 )

• 90% reduction in single positive thymocytes

• single positive splenocytes similarly reduced

hematopoietic system

abnormal thymus lobule morphology ( J:72249 )

abnormal thymus cortex morphology ( J:72249 )

• greatly expanded cortex area containing double positive cells

enlarged thymus cortex ( J:72249 )

• grossly expanded

abnormal thymus medulla morphology ( J:72249 )

• rudimentary medulla where single positive cells are located

decreased single-positive T cell number ( J:72249 )

• 90% reduction in single positive thymocytes

• single positive splenocytes similarly reduced

endocrine/exocrine glands

abnormal thymus lobule morphology ( J:72249 )

abnormal thymus cortex morphology ( J:72249 )

• greatly expanded cortex area containing double positive cells

enlarged thymus cortex ( J:72249 )

• grossly expanded

abnormal thymus medulla morphology ( J:72249 )

• rudimentary medulla where single positive cells are located

Genotype
MGI:6189180

hm4

• Allelic Composition: Hivep2^tm1Sis/Hivep2^tm1Sis
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

behavior/neurological

increased locomotor activity ( J:234969 )

• mice show increased locomotor activity in the home cage without clear infradian oscillation

nervous system

abnormal dentate gyrus morphology ( J:271912 )

• mice exhibit decreased expression levels of synaptic proteins in the dentate gyrus

abnormal hippocampus granule cell morphology ( J:271912 )

• the granule cell layer of the dentate gyrus shows a decrease in cell body size, a decrease in nuclear volume in granule cells and an increase in neuronal density

abnormal dendritic spine morphology ( J:271912 )

• granule cell dendritic spine diameter and spine neck diameter are lower

• however, spine volume and postsynaptic density area are normal

increased dendritic spine length ( J:271912 )

• granule cell dendritic spine length is increased mainly due to an increase in spine neck length

abnormal dentate gyrus neuron dendrite morphology ( J:271912 )

• mice exhibit thin dendrites with long and thin spines in granule cells in the middle molecular layer of the dorsal dentate gyrus indicating immature dendritic spine morphology

• dendrite diameter of granule cells is decreased

• filamentous mitochondria are seen in the dendritic shaft and the number of constricted mitochondria is decreased while number of elongated mitochondria is normal suggesting that the balance between mitochondrial fusion and fission is compromised

• however, no differences in mitochondria volume, length or number per 1 um of dendritic shaft are seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intellectual disability		DOID:1059		J:271912
schizophrenia		DOID:5419	OMIM:181500	J:271912

Genotype
MGI:3615665

ht5

• Allelic Composition: Hivep2^tm1Sis/Hivep2⁺
• Genetic Background: involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj

immune system

decreased CD8-positive, alpha-beta T cell number ( J:72249 )

• only CD8+ single positive splenocytes significantly reduced

decreased single-positive T cell number ( J:72249 )

• moderate reduction in single positive thymocytes

hematopoietic system

decreased CD8-positive, alpha-beta T cell number ( J:72249 )

• only CD8+ single positive splenocytes significantly reduced

decreased single-positive T cell number ( J:72249 )

• moderate reduction in single positive thymocytes

Genotype
MGI:3615666

cx6

• Allelic Composition: Hivep2^tm1Sis/Hivep2^tm1Sis; Tg(DO11.10)10Dlo/?
• Genetic Background: involves: BALB/cA * C3H * C57BL/6NCrlj * CBA/JNCrlj

immune system

abnormal positive T cell selection ( J:96024 )

• impaired positive selection

decreased single-positive T cell number ( J:72249 )

• marked reduction in CD4+ single positive t cells after ovalbumin administration relative to controls

• both CD4+ and CD8+ single positive splenocytes reduced after ovalbumin administration

abnormal T-helper 2 cell morphology ( J:96024 )

• enhanced generation of TH2 cells

• TH1 differentiation unaffected

hematopoietic system

abnormal positive T cell selection ( J:96024 )

• impaired positive selection

decreased single-positive T cell number ( J:72249 )

• marked reduction in CD4+ single positive t cells after ovalbumin administration relative to controls

• both CD4+ and CD8+ single positive splenocytes reduced after ovalbumin administration

abnormal T-helper 2 cell morphology ( J:96024 )

• enhanced generation of TH2 cells

• TH1 differentiation unaffected