Phenotypes associated with this allele

• Allele Symbol: Smarcb1^tm2Sho
• Allele Name: targeted mutation 2, Stuart Orkin
• Allele ID: MGI:2447707
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Smarcb1^tm2Sho/Smarcb1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(GFAP-cre)#Gtm/0	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA	MGI:5771803
cn2	Smarcb1^tm2Sho/Smarcb1^+ Trp53^tm1Brn/Trp53^+ Tg(GFAP-cre)#Gtm/0	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA	MGI:5771802
cn3	Smarcb1^tm2Sho/Smarcb1^tm2Sho Trp53^tm1Brn/Trp53^+ Tg(GFAP-cre)#Gtm/0	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA	MGI:5771804
cn4	Smarcb1^tm2Sho/Smarcb1^tm2Sho Trp53^tm1Brn/Trp53^tm1Brn Tg(GFAP-cre)#Gtm/0	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA	MGI:5771805
cn5	Smarcb1^tm1Sho/Smarcb1^tm2Sho Tg(Mx1-cre)1Cgn/?	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * CBA	MGI:3819384
cn6	Smarcb1^tm2Sho/Smarcb1^tm2Sho Tg(GFAP-cre)#Gtm/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:5771801
cn7	Smarcb1^tm2Sho/Smarcb1^+ Tg(Nes-cre)1Kln/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:5771800
cn8	Smarcb1^tm2Sho/Smarcb1^tm2Sho Tg(Nes-cre)1Kln/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:5771799

Genotype
MGI:5771803

cn1

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA

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

behavior/neurological

excessive scratching ( J:226786 )

• excessive scratching behavior resulting in dermatitis around the neck, earlobes, and the flank region

Genotype
MGI:5771802

cn2

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1⁺; Trp53^tm1Brn/Trp53⁺; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA

behavior/neurological

excessive scratching ( J:226786 )

• excessive scratching behavior resulting in dermatitis around the neck, earlobes, and the flank region

Genotype
MGI:5771804

cn3

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1^tm2Sho; Trp53^tm1Brn/Trp53⁺; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA

nervous system

abnormal brain white matter morphology ( J:226786 )

• lesions in the white matter of the corpus callosum and cingulum

neoplasm

neoplasm ( J:226786 )

N • no neoplastic growth is seen in the brain

Genotype
MGI:5771805

cn4

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1^tm2Sho; Trp53^tm1Brn/Trp53^tm1Brn; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 * CBA

behavior/neurological

lethargy ( J:226786 )

• many mice appear lethargic with hind limb paralysis

excessive scratching ( J:226786 )

• severe scratching behavior

dystonia ( J:226786 )

• mice exhibit intermittent episodes of tail extension and dystonic posturing of the body, frequently in response to handling

tremors ( J:226786 )

impaired coordination ( J:226786 )

• motor coordination problems become evident from around 3 weeks of age

abnormal limb posture ( J:226786 )

• abnormal posture of the hind limbs

abnormal locomotor behavior ( J:226786 )

• mice exhibit tumbling repeatedly during attempted locomotion; mice frequently fall over and repeatedly lift and replace the same paw in various positions during each stride

ataxia ( J:226786 )

• severe ataxia

abnormal gait ( J:226786 )

• mice exhibit a non-uniform gait, with uneven stride length and width, dragging of the hindpaws and an inability to keep the hindquarters upr

abnormal stride length ( J:226786 )

• uneven stride length

hindlimb paralysis ( J:226786 )

• many mice appear lethargic with hind limb paralysis

circling ( J:226786 )

seizures ( J:226786 )

• mice exhibit clear seizures or intermittent electrographic seizures associated either with forelimb clonus, evolving into body jerking, and wild running or arrest of activity during the ictal EEG discharges

cellular

abnormal cerebellar granule cell migration ( J:226786 )

• altered granule neuron migration, with some granule neurons failing to migrate out of the external germinal layer, others remaining trapped in the molecular layer

• altered cerebellar granule neuron migration is already seen at 3 weeks of age

growth/size/body

decreased body size ( J:226786 )

decreased body weight ( J:226786 )

• body weight is reduced by about 40%

mortality/aging

decreased survivor rate ( J:226786 )

• mice require water gel for survival

muscle

dystonia ( J:226786 )

• mice exhibit intermittent episodes of tail extension and dystonic posturing of the body, frequently in response to handling

neoplasm

increased brain tumor incidence ( J:226786 )

• mice develop brain tumors starting at around 1 month of age

• mice that die suddenly exhibit presence of high-grade, aggressive tumors that infiltrate and obliterate the surrounding cerebellar folia

• tumors appear to arise from the cerebellum

• tumors show hallmarks of atypical teratoid/rhabdoid tumor of the central nervous system

nervous system

seizures ( J:226786 )

• mice exhibit clear seizures or intermittent electrographic seizures associated either with forelimb clonus, evolving into body jerking, and wild running or arrest of activity during the ictal EEG discharges

abnormal cerebellar granule cell migration ( J:226786 )

• altered granule neuron migration, with some granule neurons failing to migrate out of the external germinal layer, others remaining trapped in the molecular layer

• altered cerebellar granule neuron migration is already seen at 3 weeks of age

increased brain tumor incidence ( J:226786 )

• mice develop brain tumors starting at around 1 month of age

• mice that die suddenly exhibit presence of high-grade, aggressive tumors that infiltrate and obliterate the surrounding cerebellar folia

• tumors appear to arise from the cerebellum

• tumors show hallmarks of atypical teratoid/rhabdoid tumor of the central nervous system

abnormal brain white matter morphology ( J:226786 )

• defects in white matter with complete loss of tissue in regions of white matter over time

• white matter fiber tracks are reduced

• loss of white matter is already seen at 3 weeks of age

abnormal corpus callosum morphology ( J:226786 )

• defects in the corpus callosum

• lesions in the corpus callosum are already seen at 3 weeks of age

abnormal hippocampus morphology ( J:226786 )

• defects in the hippocampus

abnormal cerebral cortex morphology ( J:226786 )

• reduced cerebral cortex is already seen at 3 weeks of age

abnormal cerebellum morphology ( J:226786 )

• defects in the cytoarchitecture of the cerebellum

• progressive loss of cells and neuronal projections in the cerebellum

abnormal cerebellum external granule cell layer morphology ( J:226786 )

• aberrant external germinal layer

abnormal cerebellar layer morphology ( J:226786 )

• the boundary between the internal granule layer and the molecular layer remains diffuse

decreased oligodendrocyte number ( J:226786 )

• loss of oligodendrocytes with age

gliosis ( J:226786 )

• high level of gliosis in the fiber tracks and in the molecular layer and in the remnants of the external germinal layer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
central nervous system cancer		DOID:3620		J:226786

Genotype
MGI:3819384

cn5

• Allelic Composition: Smarcb1^tm1Sho/Smarcb1^tm2Sho; Tg(Mx1-cre)1Cgn/?
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * CBA

mortality/aging

premature death ( J:80224 )

• 90% mortality between 1 and 3 weeks after injection with polyI/polyC

• remaining mice die over the next 4 weeks

hematopoietic system

abnormal bone marrow cell morphology/development ( J:80224 )

• deficiency of hematopoietic cells in the bone marrow

pancytopenia ( J:80224 )

• mice are ill and profoundly pancytopenic by weeks 1-2 after polyI/polyC injection

• some mice develop mild or transient pancytopenia but still experience sudden death

cardiovascular system

bruising ( J:80224 )

• extensive skin bruising

intestinal hemorrhage ( J:80224 )

digestive/alimentary system

intestinal hemorrhage ( J:80224 )

Genotype
MGI:5771801

cn6

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1^tm2Sho; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

nervous system

abnormal cerebellar granule cell migration ( J:226786 )

• variable, mild defect in granule neuron migration

abnormal brain white matter morphology ( J:226786 )

• brain lesions that are prominent in the white matter of the corpus callosum with vacuolization, spongy changes, cystic-like breakdown and destruction of tissue

• extent of damage is variable and progresses with age

abnormal corpus callosum morphology ( J:226786 )

• posterior portion of the corpus callosum is more affected than the anterior portion

thin cerebral cortex ( J:226786 )

abnormal cerebellar Purkinje cell layer ( J:226786 )

• disorganization of the Purkinje cell layer

axon degeneration ( J:226786 )

• loss of axons

demyelination ( J:226786 )

• loss of myelin

cellular

abnormal cerebellar granule cell migration ( J:226786 )

• variable, mild defect in granule neuron migration

neoplasm

neoplasm ( J:226786 )

N • mice do not develop brain tumors up to more than 1 year of age

Genotype
MGI:5771800

cn7

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * SJL

mortality/aging

prenatal lethality, incomplete penetrance ( J:226786 )

• most embryos die in utero

reproductive system

decreased litter size ( J:226786 )

Genotype
MGI:5771799

cn8

• Allelic Composition: Smarcb1^tm2Sho/Smarcb1^tm2Sho; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * SJL

mortality/aging

prenatal lethality, complete penetrance ( J:226786 )