Phenotypes Associated with This Genotype

Genotype
MGI:3712499

• Allelic Composition: Tg(Prnp-ATXN7*92Q)6076Als/0
• Genetic Background: involves: C3H/HeJ * C57BL/6

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

mortality/aging

premature death ( J:77530 )

• death between 13 and 34 weeks in most affected mice

growth/size/body

decreased body size ( J:77530 )

• most affected mice are smaller as ataxia progresses

vision/eye

abnormal retina photoreceptor morphology ( J:71971 )

decreased retina photoreceptor cell number ( J:71971 )

• retinas show increased numbers of apoptotic photoreceptor cells

absent retina cone cells ( J:71971 )

• loss of cone photoreceptors

retina photoreceptor degeneration ( J:71971 )

• photoreceptor cell degeneration: cone-rod dystrophy type of retinal degeneration

thin retina outer nuclear layer ( J:71971 )

• mutants exhibit progressive thinning of the outer nuclear layer starting at 12 weeks of age, with some regions narrowing to as few as six nuclei across

abnormal eye physiology ( J:71971 )

abnormal cone electrophysiology ( J:71971 )

• cone-initiated responses are degraded faster than rod-driven responses

• mildly affected mutants show a reduction in cone-initiated responses while maintaining normal rod responses

• moderately affected mutants show a further reduction in cone-initiated and ultimately show an absence of both the cone and rod responses to the brightest light flash

abnormal rod electrophysiology ( J:71971 )

• moderately affected mutants show a slight reduction in rod-initiated responses and ultimately show an absence of both the cone and rod responses to the brightest light flash

blindness ( J:71971 )

• age of blindness onset is 13 weeks of age

nervous system

abnormal Bergmann glial cell morphology ( J:113150 )

• increase in active caspase-3 in Bergmann glia cell bodies, indicating increased apoptosis

• Purkinje cell dendrites are surrounded by swollen Bergmann glial fibers

abnormal Purkinje cell morphology ( J:77530 )

• Purkinje cells are flattened and exhibit less dendritic arborization, and nuclei have occasional invaginations and appear granular

• however, no significant neuronal loss is observed

Purkinje cell degeneration ( J:77530 , J:113150 )

• severe Purkinje cell degeneration (smaller and shrunken) at 20 weeks of age, despite the absence of expression of the polyglutamine-expanded SCA7 in Purkinje cells (J:77530)

• 54% of Purkinje cells show increased electron density and 38% of Purkinje cells show swollen endoplasmic reticulum (ER) and rough ER denuded of ribosomes, indicating Purkinje cell degeneration (J:113150)

• dark cell degeneration of Purkinje cells (J:113150)

abnormal retina photoreceptor morphology ( J:71971 )

decreased retina photoreceptor cell number ( J:71971 )

• retinas show increased numbers of apoptotic photoreceptor cells

absent retina cone cells ( J:71971 )

• loss of cone photoreceptors

retina photoreceptor degeneration ( J:71971 )

• photoreceptor cell degeneration: cone-rod dystrophy type of retinal degeneration

abnormal glial cell physiology ( J:113150 )

• glutamate uptake capacity is reduced by approximately 40% in cerebellar synaptosomes

behavior/neurological

decreased exploration in new environment ( J:77530 )

• mutants become less explorative

increased startle reflex ( J:77530 )

• mutants startle easily

limb grasping ( J:77530 )

• 50% of 12 week old mutants are claspers in the clasping test

tremors ( J:77530 )

• mutants eventually develop a chronic whole-body tremor

abnormal motor coordination/balance ( J:77530 )

• 50% of 12 week old mutants fail in a ledge test

impaired coordination ( J:77530 )

• impairment in rotarod function by 8 weeks of age which worsens over time

abnormal locomotor behavior ( J:77530 )

ataxia ( J:77530 )

• unsteady gait progresses to a wide-based stride with occasional falling

abnormal gait ( J:77530 )

• an unsteady gait develops beginning at 8-15 weeks of age

decreased locomotor activity ( J:77530 )

• 50% of 12 week old mutants are inactive

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spinocerebellar ataxia type 7		DOID:0050958	OMIM:164500	J:71971 , J:77530 , J:113150