Phenotypes Associated with This Genotype

Genotype
MGI:5516453

• Allelic Composition: Tg(Prnp-ATXN3*70Q)70.61Olri/0
• Genetic Background: involves: C57BL/6N

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

mortality/aging

premature death ( J:122993 )

• 50% of mice survive to 3 months of age and more than 80% of mice die after 6 months of age

behavior/neurological

abnormal behavior ( J:122993 )

• mutants develop progressive neurological symptoms and severe behavioral deficits starting at 6-8 weeks of age

decreased grooming behavior ( J:122993 )

• reduction in grooming that results in a disheveled appearance

limb grasping ( J:122993 )

• 6 month old mice approaching a pen or rod from above are unable to grab it and exhibit a clasping behavior

tremors ( J:122993 )

impaired coordination ( J:122993 )

abnormal gait ( J:122993 )

• wide-based hindlimbs to stabilize the body in a resting position

• mildly affected mice at 3 months of age show a minced gait with mild disturbances and a reduced distance between each step

• at end stage of disease, mutants have a severely affected gait and are almost unable to walk

short stride length ( J:122993 )

• reduction in distance between each step

decreased locomotor activity ( J:122993 )

• mutants exhibit reduced activity, with mutants at end stage of disease almost completely inactive

growth/size/body

decreased body size ( J:122993 )

decreased body weight ( J:122993 )

nervous system

abnormal cerebellum morphology ( J:122993 )

• formation of contracted or empty baskets around Purkinje cells

abnormal Purkinje cell morphology ( J:122993 )

• shrinkage of approximately 50-80% of Purkinje cells, characterized by an increase of the electron density of the cytoplasm and the karyoplasm and by irregular alterations of the cytoplasm and nuclear shapes

neuronal intranuclear inclusions ( J:122993 )

• ataxin-3 and ubiquitin-positive neuronal intranuclear inclusion bodies are present in the brain

abnormal nervous system physiology ( J:122993 )

• content of dopamine metabolites 3,4-dihyddroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) are reduced in the striatum, however dopamine levels are normal

• turnover rate for dopamine and serotonin are reduced

skeleton

kyphosis ( J:122993 )

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:122993 )

N • normal hearing and cochlear outer hair cell function

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Machado-Joseph disease		DOID:1440	OMIM:109150	J:122993