behavior/neurological phenotype

• ataxia
  (MGI Ref ID J:133312)

• hunched posture
  (MGI Ref ID J:133312)

• head tilt
  (MGI Ref ID J:133312)

neoplasm

• increased medulloblastoma incidence
  • large tumors show areas of necrosis and neovascularization
  (MGI Ref ID J:133312)(MGI Ref ID J:189258)
  • by 5 months, incidence is >80%
  (MGI Ref ID J:133312)
  • tumors contain highly proliferative progenitor-like cells and are characterized by significant loss of neuronal differentiation
  (MGI Ref ID J:133312)
  • asymptomatic animals examined histologically at 1 and 2 months had tumor incidences of 84 and 95% respectively, with tumors localized mainly to the surface of the cerebellum
  (MGI Ref ID J:133312)
  • tumor invasion into fourth ventricle is seen in some animals
  (MGI Ref ID J:133312)
  • tumors contain polygonal to elongate cells in densely cellular sheets with rosette formation, celluar palisading, and frequent mitoses
  (MGI Ref ID J:133312)

nervous system phenotype

• abnormal cerebellum external granule cell layer morphology
  • Normal - thickness is comparable at P5
  (MGI Ref ID J:133312)
  • at P14, all mice show thickening of external granule layer (EGL) with no evidence of tumor formation at this time; thickness is 2-4 cells thick in wild-type but is 12-20 cells in transgenic cerebella
  (MGI Ref ID J:133312)

• abnormal subarachnoid space morphology
  • mice display leptomeningeal spreading tumors on brain surface and within spinal cord with foci of neoplastic cells detected in the brain distant from original tumor with vasculature often present at these sites
  (MGI Ref ID J:133312)

• abnormal cerebellum morphology
  • the cancer foci
  (MGI Ref ID J:133312)
  • transplantation of tumors to wild-type recipients result in cerebellar tumors
  (MGI Ref ID J:133312)
  • in addition to tumors seen at 1 and 2 months, animals also show ectopic granule cell rests in the superficial and midmolecular layers (in 63% of affected mice at 1 month and 68% at 2 months); such rests contain differentiated cells in contrast to cells in the cancer foci
  (MGI Ref ID J:133312)
  • medulloblastomas with cerebellar dysplasia and subsequent cerebellar effacement are observed in majority of affected mice
  (MGI Ref ID J:133312)

• increased medulloblastoma incidence
  • tumors contain polygonal to elongate cells in densely cellular sheets with rosette formation, celluar palisading, and frequent mitoses
  (MGI Ref ID J:133312)(MGI Ref ID J:189258)
  • large tumors show areas of necrosis and neovascularization
  (MGI Ref ID J:133312)
  • asymptomatic animals examined histologically at 1 and 2 months had tumor incidences of 84 and 95% respectively, with tumors localized mainly to the surface of the cerebellum
  (MGI Ref ID J:133312)
  • tumor invasion into fourth ventricle is seen in some animals
  (MGI Ref ID J:133312)
  • by 5 months, incidence is >80%
  (MGI Ref ID J:133312)
  • tumors contain highly proliferative progenitor-like cells and are characterized by significant loss of neuronal differentiation
  (MGI Ref ID J:133312)

skeleton phenotype

• abnormal cranium morphology
  (MGI Ref ID J:133312)

craniofacial phenotype

• abnormal cranium morphology
  (MGI Ref ID J:133312)

growth/size/body region phenotype

• weight loss
  (MGI Ref ID J:133312)

mammalian phenotype

• nervous system phenotype
  • Normal - mice exhibit normal cerebellum development
  (MGI Ref ID J:189258)

mortality/aging

• premature death
  • mice displaying clinical symptoms of tumor formation such as a protruding skull, head tilt, hunched posture (all suggesting hydrocephalus), ataxia (suggesting cerebellar abnormalities) or weight loss are sacrificed
  (MGI Ref ID J:133312)

mortality/aging

• premature death
  • at 8 months of age, 50% of mice have to be sacrificed due to tumor burden
  (MGI Ref ID J:221990)

neoplasm

• increased medulloblastoma incidence
  • 38% medulloblastoma incidence
  (MGI Ref ID J:221990)
  • mice start developing medullobalstoma at around 4 months of age
  (MGI Ref ID J:221990)

nervous system phenotype

• increased medulloblastoma incidence
  • mice start developing medullobalstoma at around 4 months of age
  (MGI Ref ID J:221990)
  • 38% medulloblastoma incidence
  (MGI Ref ID J:221990)

mortality/aging

• premature death
  • medulloblastoma progresses rapidly, requiring sacrifice of affected animals within 1 to 14 days of tumor onset
  (MGI Ref ID J:93861)

neoplasm

• increased medulloblastoma incidence
  • mice expressing high levels of Smoothened with the A1 point mutation develop medulloblastoma with an incidence of 48% at a median age of 25.7 weeks
  (MGI Ref ID J:93861)
  • inhibition of Notch signaling with DAPT results in a decrease in viable cell number within tumors by 48 hours of treatment
  (MGI Ref ID J:93861)
  • Normal - mice expressing Smoothened with the A2 point mutation rarely develop tumors due to low levels of transgene expression
  (MGI Ref ID J:93861)

nervous system phenotype

• abnormal subarachnoid space morphology
  • infrequent leptomeningeal spreading tumors are observed in hemizygotes
  (MGI Ref ID J:133312)

• increased medulloblastoma incidence
  • inhibition of Notch signaling with DAPT results in a decrease in viable cell number within tumors by 48 hours of treatment
  (MGI Ref ID J:93861)
  • Normal - mice expressing Smoothened with the A2 point mutation rarely develop tumors due to low levels of transgene expression
  (MGI Ref ID J:93861)
  • mice expressing high levels of Smoothened with the A1 point mutation develop medulloblastoma with an incidence of 48% at a median age of 25.7 weeks
  (MGI Ref ID J:93861)

• increased cerebellar granule cell number
  • about 80% of 8-week-old mice display extensive granule cell proliferation compared to nontransgenic controls
  (MGI Ref ID J:93861)