Phenotypes associated with this allele

• Allele Symbol: Tubb4a^em1Avan
• Allele Name: endonuclease-mediated mutation 1, Adeline Vanderver
• Allele ID: MGI:6444834
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tubb4a^em1Avan/Tubb4a^em1Avan	involves: C57BL/6	MGI:6444908
ht2	Tubb4a^em1Avan/Tubb4a^+	involves: C57BL/6	MGI:6444909

Genotype
MGI:6444908

hm1

• Allelic Composition: Tubb4a^em1Avan/Tubb4a^em1Avan
• Genetic Background: involves: C57BL/6

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

mortality/aging

premature death ( J:291062 )

• mice reach end-stage by P35-40

growth/size/body

weight loss ( J:291062 )

• mice show a gradual weight loss from P35 to P37

behavior/neurological

impaired righting response ( J:291062 )

• decreased righting reflex byP35-P40

dystonia ( J:291062 )

• mice become dystonic by around P21

tremors ( J:291062 )

• mice exhibit tremor by about P9 which progressively worsens with age

ataxia ( J:291062 )

• mice become severely ataxic by around P21

impaired coordination ( J:291062 )

• mice show a shorter latency to fall on the accelerating rotarod, which worsens over time

decreased grip strength ( J:291062 )

• mice show deficits in hanging grip strength, falling at a lesser angle

abnormal gait ( J:291062 )

• ambulatory angle is wider in mice from P14 to P35, suggesting gait instability

motor developmental delay ( J:291062 )

• mice exhibit developmental delay with persistent asymmetric limb movement and crawling gait at P10, with mice achieving walking by P14

nervous system

abnormal brain development ( J:291062 )

• mice show apoptotic oligodendrocyte precursor cells; despite ongoing loss of these cells, the total populations are stable and an increase in proliferating oligodendrocyte precursors is seen

abnormal cerebellar granule layer morphology ( J:291062 )

• severe progressive loss of the granular neuron layer from P21 to end-stage and a decrease in cerebellar volume

astrocytosis ( J:291062 )

• astrogliosis in the spinal cord

decreased oligodendrocyte number ( J:291062 )

• mice show reduced number of oligodendrocytes in the corpus callosum at P14, P21, and P35-40

abnormal axon morphology ( J:291062 )

• axon caliber in optic nerves is decreased at end-stage

• cortical neurons grown in culture exhibit shorter axon length

decreased myelin sheath thickness ( J:291062 )

• g-ratio is higher in optic nerve, indicating reduced myelin thickness

• intact axons of all calibers in optic nerves have thinner myelin sheaths

• all axons in spinal cord have thinner myelin sheaths

neuron degeneration ( J:291062 )

• progressive neuronal loss in cerebellum and striatum

• loss of striatal neurons is seen at end-stage but not at P14 and P21

axon degeneration ( J:291062 )

• optic nerves and spinal cord show axon degeneration

abnormal myelination ( J:291062 )

• myelination defects in the corpus callosum and cerebellum at P14 and P21with severely delayed myelination and with further loss of myelination at P35-P40

• optic nerves show reduced numbers of normally myelinated axons

• approximately 65% of axons in the optic nerve are unmyelinated

demyelination ( J:291062 )

• progressive demyelination over time of the optic nerve and spinal cord

dysmyelination ( J:291062 )

• mice show severe hypomyelination in the corpus callosum and cerebellum, the optic nerves and spinal cord

• about 30% of axons in the optic nerve are thinly dysmyelinated axons

muscle

dystonia ( J:291062 )

• mice become dystonic by around P21

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypomyelinating leukodystrophy 6		DOID:0060798	OMIM:612438	J:291062

Genotype
MGI:6444909

ht2

• Allelic Composition: Tubb4a^em1Avan/Tubb4a⁺
• Genetic Background: involves: C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:291062 )

N • mice exhibit a normal gait, no motor abnormalities and normal survival

nervous system

decreased myelin sheath thickness ( J:291062 )

• myelin sheaths are thinner in spinal cord

• g-ratio is higher in optic nerve, indicating reduced myelin thickness and intact axons of all calibers in optic nerves have thinner myelin sheaths

• about 5% of axons in the optic nerve are unmyelinated and about 39% are thinly myelinated

demyelination ( J:291062 )

• progressive demyelination over time of the optic nerve and spinal cord

dysmyelination ( J:291062 )

• mice show decreased myelination at 1 year of age