Phenotypes Associated with This Genotype

Genotype
MGI:6286198

• Allelic Composition: Herc2^{Gt(AR0530)Wtsi}/Herc2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

behavior/neurological

impaired coordination ( J:252045 )

• at 6 months of age, heterozygotes show a significant increase in rotarod falls relative to wild-type controls

nervous system

nervous system phenotype ( J:252045 )

N • electromyographical analysis of compound muscular action potential amplitudes in the medial gastrocnemius revealed normal neurotransmission efficacy in heterozygous mice

Purkinje cell degeneration ( J:252045 )

• at 9 months of age, heterozygotes show loss of Purkinje cells in narrow gaps at the vermis/paravermis zones or in a greater extension at the cerebellar hemispheres

• lost Purkinje cells are substituted by glial Golgi-epithelial cells and degenerative accumulations are observed within the cytoplasm of the soma and the dendrites

• Purkinje cell cytoplasm contains a high number of lysosomes, electron-dense debris, and autophagosomes with varying degrees of evolution

• damaged cisterns of Golgi apparatus and numerous cisterns of the rough endoplasmic reticulum fused to the cytoplasmic face of the nuclear membrane are observed

• degenerative signs are detected at 2 and 9 months of age, with a slight increase in the older mice

Purkinje cell axonal dystrophy ( J:252045 )

• Purkinje cell axons exhibit rounded thickenings resembling axonal torpedoes

abnormal Purkinje cell dendrite morphology ( J:252045 )

• at 9 months of age, Purkinje cell dendrites show numerous degenerative changes

cellular

abnormal lysosome morphology ( J:252045 )

• at 9 months of age, Purkinje cells exhibit significant accumulation of lysosomes in the cytoplasm and principal dendrites

abnormal autophagy ( J:252045 )

• in addition to somatic labeling, p62 immunostaining is also detected within the dendritic trees and axonal torpedoes of Purkinje cells, indicating dysregulated autophagy in Purkinje cells

• EM analysis revealed significant accumulation of autophagic and lysosomal organelles in Purkinje cells cytoplasm; this is even more pronounced in principal Purkinje cell dendrites

homeostasis/metabolism

abnormal autophagy ( J:252045 )

• in addition to somatic labeling, p62 immunostaining is also detected within the dendritic trees and axonal torpedoes of Purkinje cells, indicating dysregulated autophagy in Purkinje cells

• EM analysis revealed significant accumulation of autophagic and lysosomal organelles in Purkinje cells cytoplasm; this is even more pronounced in principal Purkinje cell dendrites