Phenotypes Associated with This Genotype

Genotype
MGI:3831004

• Allelic Composition: Tg(Neurod2-Smo*A1)199Jols/Tg(Neurod2-Smo*A1)199Jols
• Genetic Background: C57BL/6-Tg(Neurod2-Smo*A1)199Jols

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

mortality/aging

decreased tumor-free survival time ( J:133312 )

• 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

growth/size/body

weight loss ( J:133312 )

nervous system

nervous system phenotype ( J:189258 )

N • mice exhibit normal cerebellum development

increased medulloblastoma incidence ( J:133312 , J:189258 )

• by 5 months, incidence is >80% (J:133312)

• tumors contain polygonal to elongate cells in densely cellular sheets with rosette formation, celluar palisading, and frequent mitoses (J:133312)

• large tumors show areas of necrosis and neovascularization (J:133312)

• tumor invasion into fourth ventricle is seen in some animals (J:133312)

• tumors contain highly proliferative progenitor-like cells and are characterized by significant loss of neuronal differentiation (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 (J:133312)

abnormal cerebellum morphology ( J:133312 )

• medulloblastomas with cerebellar dysplasia and subsequent cerebellar effacement are observed in majority of affected mice

• 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

• transplantation of tumors to wild-type recipients result in cerebellar tumors

abnormal cerebellum external granule cell layer morphology ( 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

• thickness is comparable at P5

abnormal subarachnoid space morphology ( J:133312 )

• 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

behavior/neurological

ataxia ( J:133312 )

hunched posture ( J:133312 )

head tilt ( J:133312 )

craniofacial

abnormal cranium morphology ( J:133312 )

skeleton

abnormal cranium morphology ( J:133312 )

neoplasm

increased medulloblastoma incidence ( J:133312 , J:189258 )

• by 5 months, incidence is >80% (J:133312)

• tumors contain polygonal to elongate cells in densely cellular sheets with rosette formation, celluar palisading, and frequent mitoses (J:133312)

• large tumors show areas of necrosis and neovascularization (J:133312)

• tumor invasion into fourth ventricle is seen in some animals (J:133312)

• tumors contain highly proliferative progenitor-like cells and are characterized by significant loss of neuronal differentiation (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 (J:133312)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:189258