Phenotypes Associated with This Genotype

Genotype
MGI:5437480

• Allelic Composition: Shank2^tm1Mgle/Shank2^tm1Mgle
• Genetic Background: B6.129S4-Shank2^tm1Mgle

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

behavior/neurological

abnormal learning/memory/conditioning ( J:186718 )

• impaired spatial memory in a Morris water maze

abnormal spatial learning ( J:186718 )

• impaired spatial learning in a Morris water maze

increased anxiety-related response ( J:186718 , J:237188 )

• in males and females in an elevated plus maze (J:186718)

♂ • mice show increased anxiety-like behavior in the elevated plus maze (J:237188)

♂ • however, mice show normal behavior in the light-dark test of anxiety and mice do not show abnormalities in the hole-board test of repetitive behavior (J:237188)

increased grooming behavior ( J:186718 )

♂ • in males in a novel object recognition arena

impaired coordination ( J:237188 )

♂ • mice show increased number of missteps, fewer normal steps, and frequent back steps and jumps compared to wild-type mice in the Erasmus ladder test

abnormal voluntary movement ( J:186718 )

• when housed alone, males show enhanced jumping mostly mixed with upright scrabbling, normal grooming, and decreased digging behaviors

• females show similar repetitive jumping compared to male mice

increased locomotor activity ( J:186718 )

• in males and females in an open field test

abnormal pup retrieval ( J:186718 )

♀ • females display less efficient pup retrieval

abnormal nest building behavior ( J:186718 )

♂ • males housed alone show impaired nesting behavior

abnormal social investigation ( J:186718 )

• reduced interaction with target wild-type mice in a home cage assay

• in a 3 chamber assay preference for a novel mouse over a novel object is not as strong as in wild-type mice

• however, preference for a novel mouse over a familiar mouse is similar to wild-type

• treatment with 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) substantially improves social interaction but not other behaviors

decreased vocalization ( J:186718 )

♂ • males allowed to interact with a wild-type female vocalize less frequently and take longer to make the first call compared to wild-type males

nervous system

nervous system phenotype ( J:186718 )

N • grossly normal brain structures

N • excitatory and inhibitory synapses are similar to wild-type controls

abnormal cerebellar molecular layer ( J:237188 )

• molecular layer shows an approximate 40% reduction in the density of excitatory synapses, mainly parallel fibers-Purkinje cell synapses as shown by the reduced number of postsynaptic density apposed to presynaptic axon terminals

abnormal excitatory synapse morphology ( J:237188 )

• approximate 40% reduction in the density of excitatory synapses in the molecular layer, mainly parallel fibers-Purkinje cell synapses as shown by the reduced number of postsynaptic density apposed to presynaptic axon terminals

• brain slices show increases in the number of mismatched excitatory synapses, in which the postsynaptic density is misaligned with the presynaptic nerve terminal and free spines that are not in close contact with the presynaptic nerve terminal

• reduction in levels of excitatory synaptic proteins in the cerebellum at P19-P22

abnormal nervous system physiology ( J:186718 )

• decrease in the NMDA/AMPA ratio

reduced long-term potentiation ( J:186718 )

• long term potentiation induced by high frequency stimulation or theta burst stimulation is severely impaired

abnormal miniature excitatory postsynaptic currents ( J:237188 )

• Purkinje cells show approximate 40% reduced frequency of miniature excitatory postsynaptic currents (mEPSCs) at P19-P23

• however, mice show normal LTD at parallel fibers-Purkinje cell synapses in the cerebellum

reduced long-term depression ( J:186718 )

• long term depression induced by low frequency stimulation is completely abolished

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:186718 , J:237188