Phenotypes associated with this allele

• Allele Symbol: Shank3^tm1.2Bux
• Allele Name: targeted mutation 1.2, Joseph D Buxbaum
• Allele ID: MGI:5285394
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Shank3^tm1.2Bux/Shank3^tm1.2Bux	129S6.B6(Cg)-Shank3^tm1.2Bux	MGI:5559038
hm2	Shank3^tm1.2Bux/Shank3^tm1.2Bux	B6N.Cg-Shank3^tm1.2Bux	MGI:5559041
hm3	Shank3^tm1.2Bux/Shank3^tm1.2Bux	FVB.B6(Cg)-Shank3^tm1.2Bux	MGI:5559037
ht4	Shank3^tm1.2Bux/Shank3^+	129S6.B6(Cg)-Shank3^tm1.2Bux	MGI:5559040
ht5	Shank3^tm1.2Bux/Shank3^+	B6N.Cg-Shank3^tm1.2Bux	MGI:5559042
ht6	Shank3^tm1.2Bux/Shank3^+	C57BL/6-Shank3^tm1.2Bux	MGI:5285395

Genotype
MGI:5559038

hm1

• Allelic Composition: Shank3^tm1.2Bux/Shank3^tm1.2Bux
• Genetic Background: 129S6.B6(Cg)-Shank3^tm1.2Bux

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

mortality/aging

lethality, incomplete penetrance ( J:206790 )

• fewer than expected homozygotes (16.22%) were produced from a heterozygote x heterozygote cross

• Background Sensitivity: homozygote lethality is background dependent, the greatest loss is observed on the 129S6 background, followed by FVB/N and C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:206790 )

N • Background Sensitivity: tail flick latency is observed in mice on the C57BL/6 background, but not on FVB/N or 129S6/SvEvTac backgrounds

abnormal conditioned emotional response ( J:206790 )

• decreased freezing is observed following 3 tone-shock associations and after third association, however no significant differences are observed in contextual or cued conditioning tests

decreased anxiety-related response ( J:206790 )

• open arc entries are increased in elevated zero-maze as compared to littermate controls

decreased grip strength ( J:206790 )

• mice exhibit decrease in mean forelimb grip strength as compared to littermate controls

increased locomotor activity ( J:206790 )

• mice exhibit hyperactivity in first 10 minutes of open field test, but return to activity level similar to controls

growth/size/body

decreased body weight ( J:206790 )

• mice exhibit lower body weight than controls

Genotype
MGI:5559041

hm2

• Allelic Composition: Shank3^tm1.2Bux/Shank3^tm1.2Bux
• Genetic Background: B6N.Cg-Shank3^tm1.2Bux

mortality/aging

lethality, incomplete penetrance ( J:206790 )

• fewer than expected homozygotes (21%) were produced from a heterozygote x heterozygote cross

• Background Sensitivity: homozygote lethality is background dependent, the greatest loss is observed on the 129S6 background, followed by FVB/N and C57BL/6

behavior/neurological

decreased anxiety-related response ( J:206790 )

• mice are more active in elevated zero maze as determined by increases in total moving distance and total moving time

• open arc entries are increased in elevated zero-maze

abnormal response to novel object ( J:206790 )

• homozygous mice exhibit a preference for the unfamiliar mouse over the familiar mouse relative to littermate controls

hyporesponsive to tactile stimuli ( J:206790 )

• Background Sensitivity: mice exhibit a longer tail flick latency in the first trial of the tail-flick assay for pain sensitivity as compared to littermate controls and mice on the FVB/N and 129S6/SvEvTac backgrounds

impaired coordination ( J:206790 )

• mice exhibit a lower latency to start crossing and spent a shorter time crossing in beam walking test as compared to littermate controls

decreased vertical activity ( J:206790 )

• decreased number of rears in open field test as compared to littermate controls

decreased locomotor activity ( J:206790 )

• mice travel less in center of the open field test during first 10 minutes of test

growth/size/body

decreased body weight ( J:206790 )

• mice exhibit lower body weight than controls

Genotype
MGI:5559037

hm3

• Allelic Composition: Shank3^tm1.2Bux/Shank3^tm1.2Bux
• Genetic Background: FVB.B6(Cg)-Shank3^tm1.2Bux

mortality/aging

lethality, incomplete penetrance ( J:206790 )

• fewer than expected homozygotes (17.71%) were produced from a heterozygote x heterozygote cross

• Background Sensitivity: homozygote lethality is background dependent, the greatest loss is observed on the 129S6 background, followed by FVB/N and C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:206790 )

N • Background Sensitivity: tail flick latency is observed in mice on the C57BL/6 background, but not on FVB/N or 129S6/SvEvTac backgrounds

decreased anxiety-related response ( J:206790 )

• mice are more active in elevated zero maze as determined by increases in total moving distance and total moving time

• time spent in open arc entries is increased and in closed arcs decreased in elevated zero-maze

abnormal response to novel object ( J:206790 )

• homozygous mice exhibit a preference for the unfamiliar mouse rather than the familiar mouse as compared to littermate controls

increased vertical activity ( J:206790 )

• increased number of rears in open field test as compared to littermate controls

growth/size/body

decreased body weight ( J:206790 )

• mice exhibit lower body weight than controls

Genotype
MGI:5559040

ht4

• Allelic Composition: Shank3^tm1.2Bux/Shank3⁺
• Genetic Background: 129S6.B6(Cg)-Shank3^tm1.2Bux

behavior/neurological

decreased anxiety-related response ( J:206790 )

• open arc entries are increased in elevated zero-maze as compared to littermate controls

increased thigmotaxis ( J:206790 )

impaired coordination ( J:206790 )

• fewer mice were able to cross beam due to freezing/falls as compared to littermate controls

increased locomotor activity ( J:206790 )

• mice exhibit hyperactivity in first 10 minutes of open field test, but return to activity level similar to controls

Genotype
MGI:5559042

ht5

• Allelic Composition: Shank3^tm1.2Bux/Shank3⁺
• Genetic Background: B6N.Cg-Shank3^tm1.2Bux

behavior/neurological

decreased locomotor activity ( J:206790 )

• mice travel less in the center of the open field test during last 10 minutes of test as compared to littermate controls

Genotype
MGI:5285395

ht6

• Allelic Composition: Shank3^tm1.2Bux/Shank3⁺
• Genetic Background: C57BL/6-Shank3^tm1.2Bux

nervous system

abnormal neuron physiology ( J:175320 )

• spine enlargement accompanying long term potentiation is impaired

abnormal excitatory postsynaptic potential ( J:175320 )

• reduction in the I/O curves of field excitatory postsynaptic potentials in hippocampal slices from 3-4 week old mice

• decrease in AMPA receptor mediated field potentials

reduced long-term potentiation ( J:175320 )

• initial expression of LTP is normal but maintenance is impaired

abnormal miniature excitatory postsynaptic currents ( J:175320 )

• significantly higher frequency of miniature excitatory postsynaptic currents

decreased paired-pulse ratio ( J:175320 )

• decrease in the paired pulse ratio

behavior/neurological

abnormal social investigation ( J:175320 )

• total social sniffing by the males is lower

• however, no defect in olfactory abilities are detected

decreased vocalization ( J:175320 )

• fewer ultrasonic vocalizations emitted during male-female social interactions session

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:175320