Phenotypes Associated with This Genotype

Genotype
MGI:5800419

• Allelic Composition: Shank3^tm2.2Yhj/Shank3^tm2.2Yhj
• Genetic Background: B6.129S7(C)-Shank3^tm2.2Yhj

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

nervous system

nervous system phenotype ( J:235641 )

N • mice do not exhibit spontaneous seizures

abnormal brain white matter morphology ( J:235641 )

• reduced relative to grey matter

abnormal brain commissure morphology ( J:235641 )

• all five white matter tracts except the fornix exhibit reduced volume compared with wild-type mice

abnormal brain internal capsule morphology ( J:235641 )

• unilateral change

abnormal cerebellar peduncle morphology ( J:235641 )

• reduced

abnormal cingulum morphology ( J:235641 )

• reduced

abnormal basal ganglion morphology ( J:235641 )

• enlarged

thalamus hyperplasia ( J:235641 )

decreased amygdala size ( J:235641 )

small hippocampus ( J:235641 )

abnormal olfactory lobe morphology ( J:235641 )

• decreased size

abnormal spinal cord commissure morphology ( J:235641 )

• reduced spinal trigeminal tract

abnormal dendritic spine morphology ( J:235641 )

• decreased spine density on motor sensory neurons and striatum compared with wild-type mice

• however, spine density is normal in the hippocampus

abnormal synapse morphology ( J:235641 )

• decreased glutamatergic synapses compared with wild-type mice

• shorter and thinner striatal synapses compared with wild-type mice

abnormal nervous system electrophysiology ( J:235641 )

• altered functional connectivity in a frontostriatal circuit

abnormal single cell response ( J:235641 )

• motor sensory neurons exhibit enhanced excitability compared with wild-type mice

• however, treatment with a Grm5 positive allosteric modulate (CDPPB) rescues hyper-excitability

decreased excitatory postsynaptic current frequency ( J:235641 )

• reduced frequency in motor sensory neurons compared with wild-type mice

• treatment with a Grm5 positive allosteric modulate (CDPPB) does not change the frequency or amplitude of sEPSCs

reduced long-term depression ( J:235641 )

• following high-frequency stimulation

• however, treatment with a Grm5 positive allosteric modulate (CDPPB) rescues LTD without altering the probability of presynaptic release

behavior/neurological

abnormal behavior ( J:235641 )

• mice fail to show preference for a home nest versus an unfamiliar nest compared with wild-type mice

enhanced contextual conditioning behavior ( J:235641 )

• small enhancement

• however, mice exhibit normal cured conditioning

abnormal response to new environment ( J:235641 )

• in an arena for the novel object recognition memory test, in a novel larger arena or Morris water maze, mice try to escape the test chamber unlike wild-type mice

• however, mice placed into clean home cages do not try to escape

impaired learning ( J:235641 )

• impaired striatal learning in a bar-press food task

• however, treatment with a Grm5 positive allosteric modulate (CDPPB) partially rescues instrumental learning

impaired spatial learning ( J:235641 )

• impaired reverse learning in a Morris water maze

• however, mice exhibit normal acquisition performance in a Morris water maze and normal swimming

increased anxiety-related response ( J:235641 )

• mice spend less time in the center of the open field compared with wild-type mice

• in a light-dark emergence test, mice exhibit delayed entry into the lighted chamber and made fewer transitions between chambers compared with wild-type mice

increased grooming behavior ( J:235641 )

• mice engage in fewer of the 16 holes in a hole-board test with a tendency to re-investigate the same hole compared with wild-type mice

• mice exhibit increased grooming during social investigation tests compared with wild-type mice

• treatment with a Grm5 positive allosteric modulate (CDPPB) increases self-grooming

• however, treatment with a Grm5 antagonist (MPEP) normalizes grooming

increased startle reflex ( J:235641 )

impaired coordination ( J:235641 )

• on an accelerating and steady-speed rotarods despite normal grip strength

decreased locomotor activity ( J:235641 )

• in home cage and an open field with a tendency toward decreased rearing

• however, treatment with a Grm5 antagonist (MPEP) normalizes activity in an open field

abnormal social/conspecific interaction behavior ( J:235641 )

• mice fail to establish stable hierarchies unlike wild-type mice

abnormal social investigation ( J:235641 )

• mice exhibit longer and more frequent non-reciprocal social investigation behavior with C3H mice compared with wild-type mice

• however, mice exhibit normal levels of social interest

decreased vocalization ( J:235641 )

• fewer and shorter duration compared with wild-type mice

• lower frequencies and amplitudes of calls compared with wild-type mice

• male mice emit fewer calls with shorter duration and reduced amplitude compared with wild-type mice

• however, peak frequency is normal

hearing/vestibular/ear

abnormal ear development ( J:235641 )

• delayed ear opening at P4

integument

skin lesions ( J:235641 )

• in 16 of 30 mice at 5.5 months around the eyes, on the ears, back of the head, and under the chin of mice caused by excessive grooming

limbs/digits/tail

abnormal autopod morphology ( J:235641 )

• delayed paw position at P4

taste/olfaction

abnormal odor adaptation ( J:235641 )

• mice exhibit less robust habituation-dishabituation to olfactory stimuli compared with wild-type mice

• however, mice exhibit normal sniffing a social stimulus