Phenotypes Associated with This Genotype

Genotype
MGI:3838166

• Allelic Composition: Tg(ATXN3*)84.2Cce/0
• Genetic Background: involves: C57BL/6 * CBA

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

growth/size/body

slow postnatal weight gain ( J:76495 )

• mice have slower weight gain with a 24% weight reduction by 48 weeks of age compared to controls

• mice weigh 12% less than controls at weaning and 22% less at 20 weeks of age

weight loss ( J:76495 , J:338892 )

• mice lose weight after 30 weeks of age (J:76495)

♂ • males start to show reduced body weight after 18 weeks of age, with significant reduction by 30 weeks of age (J:338892)

behavior/neurological

hyporesponsive to tactile stimuli ( J:76495 )

• mice have reduced or no response to toe pinches with increasing age

limb grasping ( J:76495 )

• mice clasp fore- and hind-limbs when lifted by the tail

• limb clasping starts at 24 weeks of age with the forelimbs and progresses to all four limbs by 56 weeks of age in 10% of mice

tremors ( J:76495 )

• mice have mild tremors

abnormal gait ( J:76495 )

• mice have a prominent wide gait and a lowered pelvis during grid climbing

decreased locomotor activity ( J:76495 )

• mice are less active and inquisitive than controls

positive geotaxis ( J:76495 )

• mice have no negative geotaxis after 20 weeks of age

nervous system

gliosis ( J:76495 )

• mice have marked gliosis in areas of neuronal loss

decreased Purkinje cell number ( J:338892 )

• reduction in number of intact Purkinje cells in cerebellar loop IV/V to loop VIII at 18 months of age, with a tendency towards reduced numbers at 3 months

neuron degeneration ( J:76495 )

• neuronal degeneration is evident in the cerebellum

Purkinje cell degeneration ( J:76495 )

• Purkinje cell loss is evident

neuronal intranuclear inclusions ( J:76495 , J:338892 )

• is observed in >50% of pontine nuclei and >40% of dentate nuclei (J:76495)

• mice show an increase in Atxn3-positive aggregates in the brain already at 3 months of age with no further increase at 18 months of age (J:338892)

demyelination ( J:76495 )

• at 9 months of age, mice have a minor degree of de- and re- myelination in the sciatic nerves

• thin myelin is also evident in the dorsal root ganglion

cellular

gliosis ( J:76495 )

• mice have marked gliosis in areas of neuronal loss

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Machado-Joseph disease		DOID:1440	OMIM:109150	J:76495 , J:338892