Phenotypes associated with this allele

• Allele Symbol: Tg(Neurod2-Smo*A1)199Jols
• Allele Name: transgene insertion 199, James M Olson
• Allele ID: MGI:3830738
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Mir34a^tm1.2Arte/Mir34a^+ Tg(Neurod2-Smo*A1)199Jols/0	involves: C57BL/6 * C57BL/6N	MGI:5791915
cx2	Mir34a^tm1.2Arte/Mir34a^tm1.2Arte Tg(Neurod2-Smo*A1)199Jols/0	involves: C57BL/6 * C57BL/6N	MGI:5791916
tg3	Tg(Neurod2-Smo*A1)199Jols/Tg(Neurod2-Smo*A1)199Jols	C57BL/6-Tg(Neurod2-Smo*A1)199Jols	MGI:3831004
tg4	Tg(Neurod2-Smo*A1)199Jols/0	C57BL/6-Tg(Neurod2-Smo*A1)199Jols	MGI:3831003
tg5	Tg(Neurod2-Smo*A1)199Jols/0	involves: C57BL/6	MGI:5791914

Genotype
MGI:5791915

cx1

• Allelic Composition: Mir34a^tm1.2Arte/Mir34a⁺; Tg(Neurod2-Smo*A1)199Jols/0
• Genetic Background: involves: C57BL/6 * C57BL/6N

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

neoplasm

increased medulloblastoma incidence ( J:221990 )

• 75% medulloblastoma incidence

• mice show increased medulloblastoma incidence and time to tumor formation compared to single Tg(Neurod2-Smo*A1)199Jols hemizygotes

nervous system

increased medulloblastoma incidence ( J:221990 )

• 75% medulloblastoma incidence

• mice show increased medulloblastoma incidence and time to tumor formation compared to single Tg(Neurod2-Smo*A1)199Jols hemizygotes

Genotype
MGI:5791916

cx2

• Allelic Composition: Mir34a^tm1.2Arte/Mir34a^tm1.2Arte; Tg(Neurod2-Smo*A1)199Jols/0
• Genetic Background: involves: C57BL/6 * C57BL/6N

neoplasm

increased medulloblastoma incidence ( J:221990 )

• 81% medulloblastoma incidence

• mice show increased medulloblastoma incidence and time to tumor formation compared to single Tg(Neurod2-Smo*A1)199Jols hemizygotes

nervous system

increased medulloblastoma incidence ( J:221990 )

• 81% medulloblastoma incidence

• mice show increased medulloblastoma incidence and time to tumor formation compared to single Tg(Neurod2-Smo*A1)199Jols hemizygotes

Genotype
MGI:3831004

tg3

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

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

Genotype
MGI:3831003

tg4

• Allelic Composition: Tg(Neurod2-Smo*A1)199Jols/0
• Genetic Background: C57BL/6-Tg(Neurod2-Smo*A1)199Jols

mortality/aging

decreased tumor-free survival time ( J:93861 )

• medulloblastoma progresses rapidly, requiring sacrifice of affected animals within 1 to 14 days of tumor onset

neoplasm

increased medulloblastoma incidence ( 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

• mice expressing Smoothened with the A2 point mutation rarely develop tumors due to low levels of transgene expression

• inhibition of Notch signaling with DAPT results in a decrease in viable cell number within tumors by 48 hours of treatment

nervous system

increased medulloblastoma incidence ( 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

• mice expressing Smoothened with the A2 point mutation rarely develop tumors due to low levels of transgene expression

• inhibition of Notch signaling with DAPT results in a decrease in viable cell number within tumors by 48 hours of treatment

increased cerebellar granule cell number ( J:93861 )

• about 80% of 8-week-old mice display extensive granule cell proliferation compared to nontransgenic controls

abnormal subarachnoid space morphology ( J:133312 )

• infrequent leptomeningeal spreading tumors are observed in hemizygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:93861

Genotype
MGI:5791914

tg5

• Allelic Composition: Tg(Neurod2-Smo*A1)199Jols/0
• Genetic Background: involves: C57BL/6

mortality/aging

decreased tumor-free survival time ( J:221990 )

• at 8 months of age, 50% of mice have to be sacrificed due to tumor burden

neoplasm

increased medulloblastoma incidence ( J:221990 )

• mice start developing medullobalstoma at around 4 months of age

• 38% medulloblastoma incidence

nervous system

increased medulloblastoma incidence ( J:221990 )

• mice start developing medullobalstoma at around 4 months of age

• 38% medulloblastoma incidence

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:221990