growth/size/body region phenotype

• decreased body size
  • mice are smaller than wild-type littermates during first postnatal weeks, but size normalizes post-weaning
  (MGI Ref ID J:55695)

homeostasis/metabolism phenotype

• abnormal serotonin level
  • ratio of 5-hydroxyindoleacetic acid to serotonin in hippocampus are lower than in wild-type after 4 weeks of social isolation; in general, ratios are lower in mutant brains, but only significant decrease is detected in hippocampus
  (MGI Ref ID J:101930)

mammalian phenotype

• nervous system phenotype
  • Normal - dendritic and spontaneous calcium transients are similar in mutants and wild-type mice
  (MGI Ref ID J:55695)
  • Normal - pyramidal cells from hippocampal CA1 region have normal dendrites and spines, and normal morphology of excitatory synapses relative to controls
  (MGI Ref ID J:55695)

• homeostasis/metabolism phenotype
  • Normal - after 4 weeks of social isolation, dopamine levels in the brain of males are similar to controls, as are plasma testosterone levels
  (MGI Ref ID J:101930)
  • Normal - following morphine injection, both mutant and wild-type mice show similar morphine levels in brain tissue and plasma samples, indicating similar pharmacokinetics between the genotypes
  (MGI Ref ID J:75498)

• behavior/neurological phenotype
  • Normal - no deficits in spatial learning or spatial memory acquisition are observed in mutants compared to controls
  (MGI Ref ID J:55695)

nervous system phenotype

• reduced long term potentiation
  • in presence of bicuculline, LTP is absent in mutants but tetanized wild-type controls show 140% (control pathway: 100%) LTP
  (MGI Ref ID J:55695)
  • Normal - paired-pulse facilitation at CA1 excitatory synapses is similar between mutants and controls
  (MGI Ref ID J:55695)
  • in CA1 slices from adult mice, tetanization produces a persistent potentiation of synaptic responses indicated by increased average field EPSP slopes in wild-type, but mutant mice show no LTP (fEPSPs are not different from pretetanic controls
  (MGI Ref ID J:55695)

• reduced AMPA-mediated synaptic currents
  • AMPA currents measured in membrane patches from acute brain slices are strongly reduced compared to wild-type
  (MGI Ref ID J:55695)

• abnormal serotonin level
  • ratio of 5-hydroxyindoleacetic acid to serotonin in hippocampus are lower than in wild-type after 4 weeks of social isolation; in general, ratios are lower in mutant brains, but only significant decrease is detected in hippocampus
  (MGI Ref ID J:101930)

behavior/neurological phenotype

• abnormal locomotor behavior
  • duration of locomotor activity is slightly higher than controls in males kept isolated for 1, 5, or 21 days
  (MGI Ref ID J:101930)
  • increased locomotor activity response to morphine injection is greater than wild-type; however baseline values are higher than controls
  (MGI Ref ID J:75498)

• abnormal behavioral response to xenobiotic
  • unlike wild-type, mice do not show significant tolerance to the antinociceptive effect of morphine as determined by the thermal tail flick test; repeated doses with increasing doses of morphine that produce tolerance in wild-type to the antinociceptive effects still produce significant nociception in mutants
  (MGI Ref ID J:75498)
  • fects still produce significant nociception in mutants
  (MGI Ref ID J:75498)
  • animals display enhanced context-dependent sensitization to D-amphetamine compared to wild-type or Gria1^tm1Erk mice
  (MGI Ref ID J:75498)

• hyperactivity
  • slightly hyperactive in novel environment
  (MGI Ref ID J:75498)

• abnormal sexual interaction
  • males exhibit less sniffing of body of females than wild-type males
  (MGI Ref ID J:101930)

• decreased aggression towards males
  • after 30 days in isolation, male mutants do not show increased consummate aggression towards other animals when placed together, in contrast to wild-type males which show high levels of aggression towards other males
  (MGI Ref ID J:101930)
  • after pair-housing with a female for 5 days, mutants show no increased aggressive behavior toward an intruder male whereas aggression is higher in wild-type males
  (MGI Ref ID J:101930)
  • in resident-intruder test, individually tested male mice isolated for 1, 5, or 21 days show reduced frequency and duration of consummate and ambivalent aggression towards an intruder in the resident animal's cage
  (MGI Ref ID J:101930)
  • mutants show a greater duration of defensive behavior after 30 days of isolation than wild-type males
  (MGI Ref ID J:101930)

• abnormal response to new environment
  • upon repeated exposure, both mutants and wild-type show habituation but mutants still show slight difference in ambulation
  (MGI Ref ID J:75498)
  • mice are slightly hyperactive when placed in a novel cage, but do show habituation upon repeated exposure to novel cages
  (MGI Ref ID J:75498)

• increased exploration in new environment
  • male mice kept isolated for 1, 5, or 21 days show increased duration of passive exploration of environment compared to wild-type littermates
  (MGI Ref ID J:101930)

• increased vertical activity
  • rear frequency and duration are increased compared to controls in male mice isolated for 1, 5, or 21 days
  (MGI Ref ID J:101930)

• decreased behavioral withdrawal response
  • mice show a lower number of naloxone-precipitated behavioral withdrawal symptoms with chronic morphine treatment compared to wild-type littermates
  (MGI Ref ID J:75498)

• abnormal social investigation
  • frequency and duration of partner exploration are increased in male mice isolated for 1, 5, or 21 days compared to controls
  (MGI Ref ID J:101930)

• decreased anxiety-related response
  • in elevated plus-maze tests, mutant show shorter latencies to enter closed to first entry of open arms, decreased freezing and more entries into open arms compared to wild-type littermates
  (MGI Ref ID J:101930)

mammalian phenotype

• homeostasis/metabolism phenotype
  • Normal - corticosterone levels are similar in mutants as in wild-type after a single forced swim trial
  (MGI Ref ID J:167264)

behavior/neurological phenotype

• hyperactivity
  • in a novel open field
  (MGI Ref ID J:167264)

• abnormal emotion/affect behavior
  • mutants, but not wild-type mice, exhibit an increase in immobility and a decrease in swimming from trial 1 to 2 of the modified forced swim test
  (MGI Ref ID J:167264)
  • mutants exhibit a decrease in immobility compared to wild-type during the first and sometimes second forced swim trials
  (MGI Ref ID J:167264)
  • in the elevated plus-maze, mutants make more open and center entries and have more center time but less closed time, than wild-type mice
  (MGI Ref ID J:167264)
  • mutants, but not wild-type mice, exhibit a significant increase in immobility by the third forced swim trial, as compared to trial 1
  (MGI Ref ID J:167264)
  • all these behaviors are indicative of manic-like phenotype
  (MGI Ref ID J:167264)
  • mutants show less immobility and increased swimming, but no difference in climbing, in a modified forced swim test compared to wild-type mice on trial 1 but not trial 2
  (MGI Ref ID J:167264)

• increased exploration in new environment
  • mutants travel farther than wild-type mice in a novel open field
  (MGI Ref ID J:167264)
  • Normal - however, movement in a home cage-like environment is no different from wild-type
  (MGI Ref ID J:167264)

• induced hyperactivity
  • injection stress produces a transient increase in activity in mutants compared to a decrease in locomotor activity in wild-type mice
  (MGI Ref ID J:167264)
  • restraint stress produces a greater increase in locomotor activity in mutants than in wild-type mice
  (MGI Ref ID J:167264)

behavior/neurological phenotype

• abnormal emotion/affect behavior
  • lithium treatment partially rescues the elevated maze test phenotype, with mutants making fewer open entries compared to untreated mutants
  (MGI Ref ID J:167264)
  • all these behaviors are indicative of manic-like phenotype
  (MGI Ref ID J:167264)
  • in the light/dark emergence test, mutants make more shelter exits and show more frequent scanning of the shelter than wild-type, although they do not spend more time out of the shelter than wild-type mice, indicating an increase in risk assessment
  (MGI Ref ID J:167264)
  • in repeated exposure to elevated plus-maze, mutants make more open entries than wild-type, regardless of trial, and exhibit more open time; mutants make more closed arm entries on trial 2 but not trial 1
  (MGI Ref ID J:167264)
  • in the elevated plus-maze, mutants make more open and center entries and have more center time but less closed time, than wild-type mice
  (MGI Ref ID J:167264)

behavior/neurological phenotype

• abnormal nociception after inflammation
  • increased spontaneous nocifensive responses to intraplantar capsaicin, however exhibit normal spinal nociceptive tail flick reflex in response to noxious heat and hindpaw withdrawal in response to thermal or mechanical stimuli
  (MGI Ref ID J:96597)

• decreased chemical nociceptive threshold
  • reduction in nociceptive responses in phase II of formalin test and a significantly longer duration of nocifensive behaviors during phase I of formalin test
  (MGI Ref ID J:96597)

• increased anxiety-related response
  • in the elevated zero-maze, mutants make fewer open entries
  (MGI Ref ID J:167264)

integument phenotype

• decreased chemical nociceptive threshold
  • reduction in nociceptive responses in phase II of formalin test and a significantly longer duration of nocifensive behaviors during phase I of formalin test
  (MGI Ref ID J:96597)

• abnormal nociception after inflammation
  • increased spontaneous nocifensive responses to intraplantar capsaicin, however exhibit normal spinal nociceptive tail flick reflex in response to noxious heat and hindpaw withdrawal in response to thermal or mechanical stimuli
  (MGI Ref ID J:96597)

nervous system phenotype

• reduced AMPA-mediated synaptic currents
  • the AMPA/NMDA peak current ratio and current integral ratio are significantly reduced in spinal neurons
  (MGI Ref ID J:96597)
  • AMPA channel-mediated peak currents on second-order spinal neurons are significantly reduced
  (MGI Ref ID J:96597)

• abnormal spinal cord morphology
  • number of Ca²⁺-permeable AMPA channels is decreased in laminae of the spinal cord
  (MGI Ref ID J:96597)

• impaired synaptic plasticity
  • loss of acute, short-term nociceptive plasticity in the spinal dorsal horn
  (MGI Ref ID J:96597)