Phenotypes Associated with This Genotype

Genotype
MGI:6888378

• Allelic Composition: Tubb4a^Jit/Tubb4a^Jit
• Genetic Background: FVB.B6-Tubb4a^Jit

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

mortality/aging

premature death ( J:321692 )

• mice typically survive up to approximately 7 weeks

behavior/neurological

ataxia ( J:321692 )

• ataxic motor phenotypes

nervous system

increased neuron apoptosis ( J:321692 )

• loss of granule cell neurons occurs by apoptosis; increase in apoptotic cells at P21 and a highly significant increase at P35

abnormal cerebellum morphology ( J:321692 )

• cerebellar volume is reduced at P48

• however, neocortex thickness and layer organization are not different from wild-type mice

abnormal cerebellar granule cell morphology ( J:321692 )

• progressive degeneration of cerebellar granule cell neurons

• however, Purkinje cells are present similarly as in wild-type mice at P35

thin cerebellar granule layer ( J:321692 )

• progressive inner granule cell layer thinning; inner granule cell layer surface area is diminished, indicating atrophy and by P48, the inner granule layer is nearly absent with few granule cells present

• however, mice show normal size and organization of cerebellar granule cell neurons at P21, suggesting that granule cell neuron production is not affected and developmental program of granule cell neuron maturation is not affected

thin cerebellar molecular layer ( J:321692 )

• progressive molecular layer thinning

cerebellum atrophy ( J:321692 )

• reduction in size of cerebellum at P48; atrophy of the cerebellum is more severe than is accounted for by the lack of myelin

• by P35, but not at P21, the size of the cerebellum is reduced and the inner granule cell layer and molecular layer are thinner

abnormal nervous system tract morphology ( J:321692 )

• mice exhibit diminished white matter tracts at P48

neuron degeneration ( J:321692 )

• cerebellar granule cell neurons progressively degenerate between P21 and P48

abnormal oligodendrocyte physiology ( J:321692 )

• progressive cell death of oligodendrocytes

dysmyelination ( J:321692 )

• mice show a severe reduction of central myelin in all CNS regions including the forebrain and spinal cord at P48

• however, peripheral myelination is preserved

• thinned white matter tracts are evident in the corpus callosum and the spinal cord, consistent with reduced myelination

• cerebellum lacks myelin at P48

• mice show severe deficits in myelination in the corpus callosum at P21 and P48, with axons present but mostly with absent myelin sheaths

cellular

increased neuron apoptosis ( J:321692 )

• loss of granule cell neurons occurs by apoptosis; increase in apoptotic cells at P21 and a highly significant increase at P35

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypomyelinating leukodystrophy 6		DOID:0060798	OMIM:612438	J:321692