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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Hivep2tm1Sis
targeted mutation 1, Shunsuke Ishii
MGI:2182914
Summary 6 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Hivep2tm1Sis/Hivep2tm1Sis C.Cg-Hivep2tm1Sis MGI:3615668
hm2
Hivep2tm1Sis/Hivep2tm1Sis either: (involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj) or (involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj) MGI:6189202
hm3
Hivep2tm1Sis/Hivep2tm1Sis involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj MGI:3615664
hm4
Hivep2tm1Sis/Hivep2tm1Sis involves: C57BL/6NCrlj * CBA/JNCrlj MGI:6189180
ht5
Hivep2tm1Sis/Hivep2+ involves: BALB/cA * C57BL/6NCrlj * CBA/JNCrlj MGI:3615665
cx6
Hivep2tm1Sis/Hivep2tm1Sis
Tg(DO11.10)10Dlo/?
involves: BALB/cA * C3H * C57BL/6NCrlj * CBA/JNCrlj MGI:3615666


Genotype
MGI:3615668
hm1
Allelic
Composition
Hivep2tm1Sis/Hivep2tm1Sis
Genetic
Background
C.Cg-Hivep2tm1Sis
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
immune system
• enhanced generation of TH2 cells
• slightly enhanced cell division rate of CD4+ cells under conditions that enhance TH2 generation

hematopoietic system
• 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
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




Genotype
MGI:3615664
hm3
Allelic
Composition
Hivep2tm1Sis/Hivep2tm1Sis
Genetic
Background
involves: BALB/cA * 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
immune system
• greatly expanded cortex area containing double positive cells
• grossly expanded
• rudimentary medulla where single positive cells are located
• 90% reduction in single positive thymocytes
• single positive splenocytes similarly reduced

hematopoietic system
• greatly expanded cortex area containing double positive cells
• grossly expanded
• rudimentary medulla where single positive cells are located
• 90% reduction in single positive thymocytes
• single positive splenocytes similarly reduced

endocrine/exocrine glands
• greatly expanded cortex area containing double positive cells
• grossly expanded
• rudimentary medulla where single positive cells are located




Genotype
MGI:6189180
hm4
Allelic
Composition
Hivep2tm1Sis/Hivep2tm1Sis
Genetic
Background
involves: 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 show increased locomotor activity in the home cage without clear infradian oscillation

nervous system
• mice exhibit decreased expression levels of synaptic proteins in the dentate gyrus
• 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
• granule cell dendritic spine diameter and spine neck diameter are lower
• however, spine volume and postsynaptic density area are normal
• granule cell dendritic spine length is increased mainly due to an increase in spine neck length
• 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
Hivep2tm1Sis/Hivep2+
Genetic
Background
involves: BALB/cA * 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
immune system
• only CD8+ single positive splenocytes significantly reduced
• moderate reduction in single positive thymocytes

hematopoietic system
• only CD8+ single positive splenocytes significantly reduced
• moderate reduction in single positive thymocytes




Genotype
MGI:3615666
cx6
Allelic
Composition
Hivep2tm1Sis/Hivep2tm1Sis
Tg(DO11.10)10Dlo/?
Genetic
Background
involves: BALB/cA * C3H * 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)
Tg(DO11.10)10Dlo mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• impaired positive selection
• 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
• enhanced generation of TH2 cells
• TH1 differentiation unaffected

hematopoietic system
• impaired positive selection
• 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
• enhanced generation of TH2 cells
• TH1 differentiation unaffected





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
10/08/2019
MGI 6.14
The Jackson Laboratory