Phenotypes associated with this allele

• Allele Symbol: Ehmt1^tm1Yshk
• Allele Name: targeted mutation 1, Yoichi Shinkai
• Allele ID: MGI:3575505
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ehmt1^tm1Yshk/Ehmt1^tm1Yshk	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:3575661
ht2	Ehmt1^tm1Yshk/Ehmt1^+	involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj	MGI:4461144

Genotype
MGI:3575661

hm1

• Allelic Composition: Ehmt1^tm1Yshk/Ehmt1^tm1Yshk
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:97244 )

• no homozygotes born

• reduced numbers of live embryos at E9.5, none at E12.5

embryo

embryonic growth retardation ( J:97244 )

• severe growth retardation in surviving embryos at E9.5

• cell mass of E9.5 embryos 1/15 normal

open neural tube ( J:97244 )

• neural groove only closed in the tail region

incomplete somite formation ( J:97244 )

• embryos at E9.5 have reached 4-6 somite stage as opposed to 21-25 somite stage in wild-type controls

growth/size/body

embryonic growth retardation ( J:97244 )

• severe growth retardation in surviving embryos at E9.5

• cell mass of E9.5 embryos 1/15 normal

nervous system

open neural tube ( J:97244 )

• neural groove only closed in the tail region

Genotype
MGI:4461144

ht2

• Allelic Composition: Ehmt1^tm1Yshk/Ehmt1⁺
• Genetic Background: involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj

behavior/neurological

abnormal associative learning ( J:192316 )

• heterozygotes show impaired fear conditioning extinction with an increased sensitivity to external stimuli

• however, spatial learning and memory in the Barnes maze is similar to wild-type mice, even after repetitive training trials

impaired contextual conditioning behavior ( J:192316 )

• during the context phase, 24 hours after acquisition, mutants learn the association between the context and aversive stimulus, however they still show twice as much freezing as wild-type mice

• heterozygotes continue to show high freezing levels despite extinction training to tone, which does not decrease significantly over time as in wild-type mice

impaired cued conditioning behavior ( J:192316 )

• heterozygotes exhibit twice as much freezing after a footshock during the acquisition phase

• in the tone test, pre-tone freezing is higher in heterozygotes, however during tone presentations, no differences are seen

abnormal object recognition memory ( J:192316 )

• in the spatial object recognition test, heterozygotes do not spend more time exploring an object in the changed position after a 60 minute differential intertrial as do wild-type mice and show no discrimination of the displaced object

decreased exploration in new environment ( J:157021 )

• spend less time walking, rearing, or wall leaning and more time sitting in a new environment

• spend less time rearing in the light compartment and make fewer crosses between the light and dark compartments in a light-dark box

• show reduced exploration in a T maze

decreased anxiety-related response ( J:157021 )

• bury fewer marbles in a marble burying test

increased anxiety-related response ( J:157021 )

• spend less time rearing in the light compartment and make fewer crosses between the light and dark compartments in the light-dark box and in the smaller light-dark box II

• in the smaller light-dark box II mice spend less time in the light compartment

• in a mirrored chamber mice visit the rear less frequently, display a longer latency for first entry, defecate more frequently, and rear less frequently

abnormal response to novel object ( J:157021 , J:192316 )

• spend less time approaching and sniffing at novel objects (J:157021)

• in the novel object recognition test, heterozygotes do not show any preference for the new object compared with the familiar object after 10 and 80 minute differential intertrial intervals, however at 40 minute differential intertrial interval, they spend a similar amount of time exploring the new object as wild-type mice (J:192316)

decreased vertical activity ( J:157021 )

• spend less time rearing, or wall leaning and more time sitting in a new environment

• spend less time rearing in the light compartment of a dark-light box, i a mirrored chamber and in a T maze

decreased locomotor activity ( J:157021 )

• spend less time walking and more time sitting in a new environment

• show reduced activity in a T maze

abnormal sensory capabilities/reflexes/nociception ( J:192316 )

• heterozygotes exhibit increased freezing levels during acquisition and context testing, however the context test freezing levels are comparable with their respective acquisition freezing levels indicating that most likely, mutants show increased sensitivity to sensory stimuli

increased startle reflex ( J:192316 )

• heterozygotes show 60% increase in startle responses for 110, 120 and 130 dB pulses compared with wild-type

• auditory brainstem response indicates that hearing is normal

abnormal social/conspecific interaction behavior ( J:157021 )

• in a social play test male mice spend less time socially exploring, pouncing and following another mouse

• in a sociability test mice demonstrate a preference for the stranger during the 5-10 min period in contrast wild-type mice no longer show a preference during this time period indicating a prolonged sociability response

abnormal social investigation ( J:157021 )

• in a social play test male mice spend less time socially exploring

• display a delayed or absent preference for social novelty in a 2 stranger test

nervous system

abnormal hippocampus pyramidal cell morphology ( J:192316 )

• hippocampal CA1 pyramidal neurons show a reduced total length, reduced number of branch parts, reduction in the highest branch order, reduced number of endings and smaller total surface area of the apical dendrite, indicating reduced dendritic arborization

abnormal dendrite morphology ( J:192316 )

• hippocampal neurons show reduced dendritic arborization and decreased spine density

abnormal dendritic spine morphology ( J:192316 )

• hippocampal CA1 neurons from secondary and tertiary branches of the apical dendrite show a 15% reduction in the spine density, in particular the stubby and mushroom type spines

impaired synaptic plasticity ( J:192316 )

• heterozygotes show altered short-term plasticity as indicated by increased paired-pulse facilitation and reduced mEPSC frequency

• however, basal synaptic transmission is normal and no changes in LTP are seen in the hippocampus

abnormal miniature excitatory postsynaptic currents ( J:192316 )

• hippocampal neurons show a decrease in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in the presence of tetrodotoxin, picrotoxin and AP-5, however the amplitude is not affected

enhanced paired-pulse facilitation ( J:192316 )

• hippocampal neurons show increased paired-pulse facilitation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Kleefstra syndrome 1		DOID:0060352	OMIM:610253	J:157021 , J:192316