Phenotypes associated with this allele

• Allele Symbol: Shank3^tm1.1Pfw
• Allele Name: targeted mutation 1.1, Paul Worley
• Allele ID: MGI:5085999
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Shank3^tm1.1Pfw/Shank3^tm1.1Pfw	B6.129S6-Shank3^tm1.1Pfw	MGI:5563203
ht2	Shank3^tm1.1Pfw/Shank3^+	B6.129S6-Shank3^tm1.1Pfw	MGI:5086221

Genotype
MGI:5563203

hm1

• Allelic Composition: Shank3^tm1.1Pfw/Shank3^tm1.1Pfw
• Genetic Background: B6.129S6-Shank3^tm1.1Pfw

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

behavior/neurological

behavior/neurological phenotype ( J:204162 )

N • do not show communication deficits or abnormalities in startle response

photophobia ( J:204162 )

• remarkable increase in avoidance of a brightly lit chamber in a dark/light chamber assay spending almost the entire 10 min assay time in the dark chamber

• however, mice do not show increased anxiety-like behaviors in elevated plus maze or open field assays, suggesting this is an avoidance of light rather than an anxiety-like behavior

impaired spatial learning ( J:204162 )

• in a Morris water maze

• in a reversal learning water maze test mice fail to show any preference for the new target location in the probe trial

abnormal spatial reference memory ( J:204162 )

• in a reversal learning water maze test mice fail to show any preference for the new target location in the probe trial

abnormal innate avoidance response ( J:204162 )

• remarkable increase in avoidance of a brightly lit chamber in a dark/light chamber assay spending almost the entire 10 min assay time in the dark chamber

• however, mice do not show increased anxiety-like behaviors in elevated plus maze or open field assays, suggesting this is an avoidance of light rather than an anxiety-like behavior

abnormal response to novelty ( J:204162 )

• show no preference for social novelty versus familiarity

decreased exploration in new environment ( J:204162 )

• decrease locomotor behavior for the first 5 min in a novel home cage, this rapidly reverts to wild-type levels after the first 5 min

abnormal response to novel object ( J:204162 )

• fail to interact with inanimate objects in nest building and marble burying assays

• interact significantly less with an inanimate object in a three-chamber social interaction assay

increased grooming behavior ( J:204162 )

• increase in grooming and time spent per grooming bout in older (10-13 months of age) but not younger (9-18 weeks of age) mice

abnormal motor coordination/balance ( J:204162 )

♀ • increased swim speed in females

impaired coordination ( J:204162 )

• decrease in latency to fall in a rotarod assay

decreased thermal nociceptive threshold ( J:204162 )

• decreased latency in a hotplate assay

abnormal social investigation ( J:204162 )

• show no preference for social novelty versus familiarity

nervous system

nervous system phenotype ( J:204162 )

N • the number and structure of CA1 pyramidal neuron synaptic spines are similar to controls

abnormal excitatory postsynaptic currents ( J:204162 )

• the input/output relationship of stimulus intensity to slope of the fEPSP is decreased

abnormal glutamate-mediated receptor currents ( J:204162 )

• decrease in the NMDA/AMPA ratio in hippocampal synapses

reduced long-term potentiation ( J:204162 )

• significantly impaired

abnormal miniature excitatory postsynaptic currents ( J:204162 )

• frequency is significantly decreased; however, amplitude is similar to controls

growth/size/body

decreased body weight ( J:204162 )

• at about 17 weeks of age

homeostasis/metabolism

photophobia ( J:204162 )

• remarkable increase in avoidance of a brightly lit chamber in a dark/light chamber assay spending almost the entire 10 min assay time in the dark chamber

• however, mice do not show increased anxiety-like behaviors in elevated plus maze or open field assays, suggesting this is an avoidance of light rather than an anxiety-like behavior

vision/eye

photophobia ( J:204162 )

• remarkable increase in avoidance of a brightly lit chamber in a dark/light chamber assay spending almost the entire 10 min assay time in the dark chamber

• however, mice do not show increased anxiety-like behaviors in elevated plus maze or open field assays, suggesting this is an avoidance of light rather than an anxiety-like behavior

Genotype
MGI:5086221

ht2

• Allelic Composition: Shank3^tm1.1Pfw/Shank3⁺
• Genetic Background: B6.129S6-Shank3^tm1.1Pfw

behavior/neurological

behavior/neurological phenotype ( J:198768 )

N • mice exhibit normal short-term spatial recognition, spatial working memory, context and cue-related fear memory and extinction, anxiety levels, and learning of motor skills

decreased startle reflex ( J:198768 )

• mice exhibit lower amplitudes and longer latencies of startle response compared with wild-type mice

induced hyperactivity ( J:198768 )

• in dizocilpine- or amphetamine-treated mice

• however, mice do not exhibit novelty-induced hyperactivity

abnormal social/conspecific interaction behavior ( J:198768 )

• mice exhibit reduced social investigation modulated by episodes of aggression compared with wild-type mice

increased aggression towards mice ( J:198768 )

• mice exhibit increased aggression towards a novel stimulus mouse and in a resident-intruder tests compared with wild-type mice

abnormal social investigation ( J:198768 )

• mice exhibit reduced social investigation modulated by episodes of aggression compared with wild-type mice

• male mice spend more time investigating an enclosed male stimulus compared with wild-type mice

• male mice exhibit increased latency to approach a sexually receptive enclosed female mouse compared with wild-type mice

• however, mice exhibit normal social recognition memory

abnormal vocalization ( J:198768 )

♂ • male mice exhibit latency to first ultrasound call in the presence of a female mice compared with wild-type mice

nervous system

abnormal glutamate-mediated receptor currents ( J:198768 )

• the ratio of NMDA to AMPA-dependent response in the cortex is reduced compared to in wild-type mice

• however, AMPAR-mediated miniature excitatory postsynaptic current amplitude and frequency are normal

reduced NMDA-mediated synaptic currents ( J:198768 )

reduced long-term potentiation ( J:198768 )

• NMDAR-dependent long term potentiation induction magnitude is reduced and decays more rapidly than in wild-type mice

abnormal long-term depression ( J:198768 )

• glutamate receptor long term depression (mGluR-LTD) induced by DHPG is increased and inhibited by cycloheximide compared to in wild-type mice

• LTD induced by paired-pulse low-frequency stimulation is increased compared to in wild-type mice

decreased synaptic depression ( J:198768 )

• NMDAR-dependent long term depression of Schaffer collateral-CA1 synapses is reduced compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:198768