homeostasis/metabolism phenotype

• abnormal autophagy
  • accumulation of lipid droplets and damaged mitochondria in primary neuronal cultures, indicating impaired autophagy
  (MGI Ref ID J:217829)
  • basal autophagy is suppressed in the brain
  (MGI Ref ID J:217829)
  • Normal - rapamycin treatment normalizes autophagy
  (MGI Ref ID J:217829)

nervous system phenotype

• abnormal dendritic spine morphology
  • density of dendritic spines in pyramidal neuron basal dendrites of layer V A1/S2 in temporal cortex is increased in adolescent males
  (MGI Ref ID J:217829)
  • Normal - mice treated with an intraperitoneal injection of rapamycin show a correction of the pruning defect
  (MGI Ref ID J:217829)
  • similar numbers of spines are seen at P19-P20 as in wild-type mice but far more spines in P29-P30 mutants, indicating a lack of normal spine pruning, with only 26% of spines being pruned
  (MGI Ref ID J:217829)

behavior/neurological phenotype

• abnormal response to novel object
  • male adolescent mice spend less time exploring the novel object than wild-type mice in the novel object recognition test
  (MGI Ref ID J:217829)
  • Normal - however, male adolescent mice do not exhibit repetitive behaviors, motor defects or anxiety-like behaviors in the open field
  (MGI Ref ID J:217829)

• abnormal response to social novelty
  • male adolescent (P30-P35) mice spend less time sniffing the stimulus mouse during a dyadic social interaction with a novel mouse, indicating impaired social interactions
  (MGI Ref ID J:217829)
  • in the social novelty test, adolescent males spend a similar amount of time sniffing both novel and familiar targets, with decreased preference index (the ratio of time sniffing a stranger mouse versus a familiar mouse), indicating a reduced preference for social novelty
  (MGI Ref ID J:217829)

• abnormal social investigation
  • in the three-chamber social test, male adolescent mice show a preference for interacting with a social target compared with nonsocial target, and the preference index (the ratio of time sniffing mouse versus nonsocial target) is decreased
  (MGI Ref ID J:217829)
  • Normal - treatment with rapamycin rescues social deficits (normalizes sociability and social novelty preferences
  (MGI Ref ID J:217829)

cellular phenotype

• abnormal autophagy
  • Normal - rapamycin treatment normalizes autophagy
  (MGI Ref ID J:217829)
  • accumulation of lipid droplets and damaged mitochondria in primary neuronal cultures, indicating impaired autophagy
  (MGI Ref ID J:217829)
  • basal autophagy is suppressed in the brain
  (MGI Ref ID J:217829)

liver/biliary system phenotype

• increased hepatic hemangioma incidence
  • 50% incidence; causes fatal bleeding in 10% of these cases
  (MGI Ref ID J:57631)

renal/urinary system phenotype

• increased renal carcinoma incidence
  • less than 10% incidence
  (MGI Ref ID J:57631)

• increased renal cystadenoma incidence
  • 100% incidence
  (MGI Ref ID J:57631)

respiratory system phenotype

• increased lung adenoma incidence
  • 32% incidence
  (MGI Ref ID J:57631)

neoplasm

• increased lung adenoma incidence
  • 32% incidence
  (MGI Ref ID J:57631)

• increased extremity angiosarcoma incidence
  • less than 10% incidence
  (MGI Ref ID J:57631)

• increased tumor incidence
  • note that the tumor expression pattern is influenced by genetic background; authors note fewer large renal cystadenomas in outbred Black Swiss background and more angiosarcomas in 129S4/SvJae chimeric mice
  (MGI Ref ID J:57631)
  • Background Sensitivity - note that the tumor expression pattern is influenced by genetic background; authors note fewer large renal cystadenomas in outbred Black Swiss background and more angiosarcomas in 129S4/SvJae chimeric mice
  (MGI Ref ID J:57631)
  • reported at 15 months of age
  (MGI Ref ID J:57631)

• increased renal cystadenoma incidence
  • 100% incidence
  (MGI Ref ID J:57631)

• increased hepatic hemangioma incidence
  • 50% incidence; causes fatal bleeding in 10% of these cases
  (MGI Ref ID J:57631)

• increased renal carcinoma incidence
  • less than 10% incidence
  (MGI Ref ID J:57631)

behavior/neurological phenotype

• abnormal spatial learning
  • in a hippocampus-dependent version of the Morris water maze test, spatial learning is impaired compared to in wild-type mice
  (MGI Ref ID J:138621)
  • mice exhibit more across-phase errors compared to in wild-type mice in a hippocampus-dependent win-shift version of the eight-arm radial maze
  (MGI Ref ID J:138621)
  • Normal - however, spatial learning in a hippocampus-independent water maze is normal and treatment with rapamycin re-establishes normal spatial learning
  (MGI Ref ID J:138621)

• abnormal contextual conditioning behavior
  • following contextual conditioning, mice exhibit reduced freezing compared to wild-type mice
  (MGI Ref ID J:138621)
  • Normal - however, treatment with rapamycin re-establishes normal contextual conditioning
  (MGI Ref ID J:138621)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - mice exhibit normal motor skills, exploratory behavior, anxiety and social approach behavior
  (MGI Ref ID J:138621)

• nervous system phenotype
  • Normal - mice exhibit normal basal synaptic transmission, paired-pulse facilitation and early-phase long term potentiation
  (MGI Ref ID J:138621)

nervous system phenotype

• enhanced long term potentiation
  • Normal - however, treatment with rapamycin re-establishes normal late-phase long term potentiation
  (MGI Ref ID J:138621)
  • mice exhibit lowered late-phase threshold for long term potentiation compared to in wild-type mice
  (MGI Ref ID J:138621)

liver/biliary system phenotype

• liver hypoplasia
  (MGI Ref ID J:57631)

mortality/aging

• embryonic lethality during organogenesis, complete penetrance
  • age of onset E9.5
  (MGI Ref ID J:57631)