Phenotypes associated with this allele

• Allele Symbol: Atxn3⁺
• Allele Name: wild type
• Allele ID: MGI:2434854
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Atxn3^em1Jhus/Atxn3^+	C57BL/6-Atxn3^em1Jhus	MGI:8250250
ht2	Atxn3^em2Jhus/Atxn3^+	C57BL/6-Atxn3^em2Jhus	MGI:8250318
ht3	Atxn3^tm2.1(ATXN3*)Mfig/Atxn3^+	involves: 129 * C57BL/6J	MGI:5750701
ht4	Atxn3^tm1Hlp/Atxn3^+	involves: C57BL/6	MGI:5688780

Genotype
MGI:8250250

ht1

• Allelic Composition: Atxn3^em1Jhus/Atxn3⁺
• Genetic Background: C57BL/6-Atxn3^em1Jhus

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

growth/size/body

weight loss ( J:338892 )

• mice have a significant reduction in body weight starting at 48 weeks of age which is more pronounced in males than females

• at 18 months of age, males have an approximate weight reduction of 24%

behavior/neurological

impaired coordination ( J:338892 )

♀ • females show a tendency for coordination deficits on the rotarod at 3 months which becomes significant at 18 months

abnormal gait ( J:338892 )

• gait analysis shows that the right hind paw has an increased step cycle (the time it takes to remove the paw from the surface and to place it back) in 18-month-old mice

• the base of support of the hind paws (distance between the left and right hind paw) is increased in 18-month-old mice, indicating the need of a wider stand for stabilization, however base of support of the front paws is not different

nervous system

decreased Purkinje cell number ( J:338892 )

• reduction in number of intact Purkinje cells in cerebellar loop IV/V to loop VIII at 12 and 18 months of age, with a tendency towards reduced numbers at 3 months

neuronal intranuclear inclusions ( J:338892 )

• mice show an increase in ubiquitin-positive and Atxn3-positive aggregates in all areas of the brain within 18 months, with mice showing the formation of aggregates in the hippocampus already at 3 months of age

skeleton

kyphosis ( J:338892 )

• mice develop hunchback posturing

Genotype
MGI:8250318

ht2

• Allelic Composition: Atxn3^em2Jhus/Atxn3⁺
• Genetic Background: C57BL/6-Atxn3^em2Jhus

normal phenotype

no abnormal phenotype detected ( J:338892 )

• neither Atxn2- nor ubiquitin-positive aggregates are seen in the brain at 8 or 18 months of age, and mice show normal weight and gait

Genotype
MGI:5750701

ht3

• Allelic Composition: Atxn3^{tm2.1(ATXN3*)Mfig}/Atxn3⁺
• Genetic Background: involves: 129 * C57BL/6J

behavior/neurological

impaired coordination ( J:218541 )

• mice show impaired performance on the rotarod at 90 weeks of age

• mutants show increased latency to turn 180 degrees on the static rod apparatus compared to wild-type mice

nervous system

astrocytosis ( J:218541 )

• 12 month old mice show increased astrogliosis in the cerebellar white matter and substantia nigra of the midbrain

abnormal Purkinje cell morphology ( J:218541 )

• Purkinje cell bodies are smaller and irregular

• Purkinje cells with more than one dendrite are seen in mutants but rarely in wild-type mice

decreased Purkinje cell size ( J:218541 )

neuronal cytoplasmic inclusions ( J:218541 )

• perinuclear inclusions containing polyQ protein are seen in various brain regions, including the cerebellum, the cerebral cortex, and the hippocampus

neuronal intranuclear inclusions ( J:218541 )

• intranuclear inclusions containing polyQ protein are seen in various brain regions, including the cerebellum, the cerebral cortex, and the hippocampus

neurodegeneration ( J:218541 )

• mice exhibit cerebellar neurodegeneration

Purkinje cell degeneration ( J:218541 )

• mild loss of Purkinje cells in the nodular zone and the anterior region

cellular

astrocytosis ( J:218541 )

• 12 month old mice show increased astrogliosis in the cerebellar white matter and substantia nigra of the midbrain

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Machado-Joseph disease		DOID:1440	OMIM:109150	J:218541

Genotype
MGI:5688780

ht4

• Allelic Composition: Atxn3^tm1Hlp/Atxn3⁺
• Genetic Background: involves: C57BL/6

nervous system

neuronal cytoplasmic inclusions ( J:219232 )

• ubiquitin-positive extranuclear neuronal aggregates in the brain, especially in the stratum radiatum of the hippocampus, the subiculum, central amygdala and bed nucleus of the stria terminalis that are localized to neuritic processes

• extranuclear inclusions are seen as small puncta in the hippocampal neuropil at 3 months of age and grow over time into large, irregular structures by 1 year of age

neuronal intranuclear inclusions ( J:219232 )

• mice exhibit intranuclear accumulation of the mutant Atxn3 protein in the brain by 10 weeks of age and abundant nuclear inclusions

• however, degenerative changes in the brain are not seen

behavior/neurological

behavior/neurological phenotype ( J:219232 )

N • mice exhibit normal fear conditioning to shock