Phenotypes Associated with This Genotype

Genotype
MGI:5696777

• Allelic Composition: Afg3l2^Emv66/Afg3l2⁺
• Genetic Background: involves: MEV/2Ty

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

behavior/neurological

limb grasping ( J:151797 )

• mice show limb clasping on tail suspension beginning at 8-10 months of age, with 84.7% of mice showing clasping by 12 months

impaired balance ( J:151797 )

• 4 month old mutants can hardly walk along a beam and make more foot slips compared to wild-type mice

impaired coordination ( J:151797 )

• mice fail to maintain balance on the rotarod at 4 months; performance worsens with age

• when traversing a beam, mutants flatten their abdomen and thorax against the upper surface of the beam instead of adapting a stable upright posture as in wild-type mice

• mutants show increased latency to cross a beam

abnormal locomotor activation ( J:151797 )

• negative-geotaxis reflex is seen at 4 months of age and worsens with age

abnormal gait ( J:151797 )

• altered gait is seen at 4 months of age and worsens with age, such that 12 month old mutants show uncoordinated hindlimb movement

• pelvic elevation is seen at 12 months of age and worsens with age

nervous system

abnormal neuron mitochondrial morphology ( J:151797 )

Purkinje cell degeneration ( J:151797 )

• progressive degeneration and loss of Purkinje cell in the cerebella, beginning at 4 months of age

• Purkinje cells undergo dark cell degeneration, characteristic of excitotoxic injury

• however, motoneuron degeneration in the spinal cord is not seen

abnormal Purkinje cell dendrite morphology ( J:151797 )

• dendritic stalks are abbreviated and hypertrophic with poorly arborized dendritic branches

• enlarged, vacuolated mitochondria in Purkinje cell dendrites

abnormal cerebellar granule layer morphology ( J:151797 )

• at 12 months, mitochondria with destroyed cristae, and organelles with unusual shapes and spatial organization are seen in the granule cell layer

abnormal cerebellar granule cell morphology ( J:151797 )

• aberrant mitochondria are seen in the granule cell layer at 4 months age, the number of which increases over time

• granule cells progressively deteriorate such that at 6 months, many cells show empty cytoplasm and nucleus with condensed chromatin, features of late-stage apoptosis

thin cerebellar granule layer ( J:151797 )

• at 6 and 12 months of age

thin cerebellar molecular layer ( J:151797 )

• reduction in molecular layer thickness at 6 months of age, consisting mostly of Purkinje cell dendrites

gliosis ( J:151797 )

• extensive reactive gliosis in the granule cell layer at 12 months of age

astrocytosis ( J:151797 )

• cerebella exhibits activated astrocytes

cellular

abnormal mitochondrial morphology ( J:151797 )

• Purkinje cells and granule cells show defects in mitochondrial morphology, distribution, and cristae organization by 4 months of age

abnormal mitochondrial crista morphology ( J:151797 )

• cristae structure is abnormal in Purkinje cells and granule cells

abnormal neuron mitochondrial morphology ( J:151797 )

increased mitochondrial size ( J:151797 )

• mitochondria in Purkinje cells and granule cells are larger

abnormal respiratory electron transport chain ( J:151797 )

• Purkinje cells show impaired mitochondrial bioenergetics, with a deficiency in respiratory chain complexes I and III, leading to increased levels of protein carbonylation and mitochondrial reactive oxygen species production

abnormal mitochondrial ATP synthesis coupled electron transport ( J:151797 )

• mice show reduced ATP synthesis in mitochondria from cerebellum, but not from entire brain or spinal cord, at 6 months with pyruvate, glutamate, and succinate/rotenone, which becomes more severe at 12 months of age

oxidative stress ( J:151797 )

• Purkinje cells show increased reactive oxygen species production

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spinocerebellar ataxia type 28		DOID:0050977	OMIM:610246	J:151797