cellular phenotype

• abnormal neuronal migration
  • at E15, fewer neurons enter the cerebral wall compared to in wild-type mice
  (MGI Ref ID J:121219)

behavior/neurological phenotype

• abnormal contextual conditioning behavior
  • a significantly higher her percentage of contextual freezing responses is observed for up to 90 days
  (MGI Ref ID J:67395)
  • 3-5 month old mice exhibit delayed extinction of conditioned fear responses compared to wild-type; mice display normal acquisition of contextual fear conditioning; null mice do not show a decline in freeaing responses over three days as do the wild-type; a significantly higher her percentage of contextual freezing responses is observed for up to 90 days
  (MGI Ref ID J:67395)

• abnormal spatial learning
  • in trials with a visual cue of the platform location, null mice showed longer escape latencies during trials 4-12, then showed similar performance to conrols
  (MGI Ref ID J:102603)
  • in a second probe trial with the platform removed, the time spent in the target quadrant by null mice is 31% compared to 50% by controls and had a reduced number of annulus crossings through the former location of the platform
  (MGI Ref ID J:102603)
  • 3-5 month old null mice exhibit a spatial learning deficit as shown by longer latencies to locate a hidden platform in the initial acquisition phase
  (MGI Ref ID J:102603)
  • in a Morris water maze
  (MGI Ref ID J:102600)
  • in the first probe trial with an absent platform conducted 24 hours after the acquisiton trials, null mice display less selective searching behavior for an absent platform and less time in the target quadrant (40% for control, 27% for nulls); on reversal trials with the platform in a new location, null animals have longer escape latencies than control over the course of 12 trials
  (MGI Ref ID J:102603)
  • trials with the platform in a new location, null animals have longer escape latencies than control over the course of 12 trials
  (MGI Ref ID J:102603)

• abnormal inhibitory learning
  • on reversal trials with the platform in a new location, null animals have longer escape latencies than control over the course of 12 trials
  (MGI Ref ID J:102603)

• abnormal passive avoidance behavior
  • after confinement for 1 minute to the shock-paired chamber, null mice show less of a decline in latency to enter the conditioning chamber compared to wild-type
  (MGI Ref ID J:67395)
  • 3-5 month old nulls maintain enhanced step-through latencies for up to 45 days post shock-conditioning
  (MGI Ref ID J:67395)

• impaired coordination
  • compared with wild-type mice
  (MGI Ref ID J:102600)

• behavioral despair
  • mice tend to float in the water instead of swimming compared with wild-type mice
  (MGI Ref ID J:102600)

• increased thigmotaxis
  • in the water
  (MGI Ref ID J:102600)

• decreased vertical activity
  (MGI Ref ID J:102600)

• hypoactivity
  • in an open field compared with wild-type mice
  (MGI Ref ID J:102600)

growth/size/body region phenotype

• decreased body size
  • nulls are 20-30% smaller than heterozygotes or wild-type
  (MGI Ref ID J:67395)(MGI Ref ID J:102603)

nervous system phenotype

• loss of GABAergic neurons
  • at E15, GABA+ cell density in the ventral zone/subventricular zone is decreased 53% compared to in wild-type mice
  (MGI Ref ID J:121219)
  • at E15, GABA+ cell density is decreased in the intermediate zone 48% compared to in wild-type mice
  (MGI Ref ID J:121219)
  • at E15, the number of GABA+ cells is decreased 25% in the presumptive medial prefrontal cortex compared to in wild-type mice
  (MGI Ref ID J:121219)
  • Normal - however, the numbers of GABA+ cells in the marginal zone and subplate/cortical plate are normal
  (MGI Ref ID J:121219)

• abnormal neuronal migration
  • at E15, fewer neurons enter the cerebral wall compared to in wild-type mice
  (MGI Ref ID J:121219)

behavior/neurological phenotype

• hunched posture
  • by weaning, mice have hunched posture
  (MGI Ref ID J:22076)

• decreased vertical activity
  • 5-6 week old mutants exhibit significantly fewer rearing events than wild-type
  (MGI Ref ID J:22076)

growth/size/body region phenotype

• postnatal growth retardation
  • mice are normal with respect to wild-type up to 2 weeks of age, but are significantly growth retarded by weaning age; mice appear sickly and majority do not gain weight
  (MGI Ref ID J:22076)

• decreased body weight
  • mice that are separated from heterozygous and wild-type littermates fed moistened lab chow appear healthy but only gain 70% of weight that sex-matched littermates reach by 6 weeks of age
  (MGI Ref ID J:22076)

integument phenotype

• disheveled coat
  • by weaning, mice have poorly groomed coat
  (MGI Ref ID J:22076)

mortality/aging

• premature death
  • majority of mice die within 1 week after weaning unless given hydrated food
  (MGI Ref ID J:22076)

behavior/neurological phenotype

• abnormal contextual conditioning behavior
  • 3-5 month old mice exhibit delayed extinction of conditioned fear responses compared to wild-type; mice display normal acquisition of contextual fear conditioning; null mice do not show a decline in freeaing responses over three days as do the wild-type; a significantly higher her percentage of contextual freezing responses is observed for up to 90 days
  (MGI Ref ID J:67395)
  • a significantly higher her percentage of contextual freezing responses is observed for up to 90 days
  (MGI Ref ID J:67395)

• abnormal passive avoidance behavior
  • after confinement for 1 minute to the shock-paired chamber, 3 to 5 month old heterozygous mice show less of a decline in latency to enter the conditioning chamber compared to wild-type
  (MGI Ref ID J:67395)

behavior/neurological phenotype

• decreased response to stress-induced hyperthermia
  • methamphetamine-treated mice exhibit less of an increase in body temperature compared with similarly treated wild-type mice
  (MGI Ref ID J:137069)

homeostasis/metabolism phenotype

• decreased physiological sensitivity to xenobiotic
  • methamphetamine-treated mice exhibit less of an increase in body temperature compared with similarly treated wild-type mice
  (MGI Ref ID J:137069)

• decreased response to stress-induced hyperthermia
  • methamphetamine-treated mice exhibit less of an increase in body temperature compared with similarly treated wild-type mice
  (MGI Ref ID J:137069)

• decreased sensitivity to xenobiotic induced morbidity/mortality
  • 7% of methamphetamine-treated mice die compared with 27% of similarly treated wild-type mice
  (MGI Ref ID J:137069)

mortality/aging

• decreased sensitivity to xenobiotic induced morbidity/mortality
  • 7% of methamphetamine-treated mice die compared with 27% of similarly treated wild-type mice
  (MGI Ref ID J:137069)

vision/eye phenotype

• abnormal vision
  • visual acuity is reduced
  (MGI Ref ID J:185955)
  • small increase in contrast sensitivity at high spatial frequencies
  (MGI Ref ID J:185955)

• abnormal eye electrophysiology
  • baseline amplitude of the light-adapted electroretinographic response is reduced
  (MGI Ref ID J:185955)

behavior/neurological phenotype

• increased startle reflex
  • mice exhibit increased acoustic startle response amplitude compared with wild-type mice
  (MGI Ref ID J:154428)