Phenotypes associated with this allele

• Allele Symbol: Herc2^{Gt(AR0530)Wtsi}
• Allele Name: gene trap AR0530, Wellcome Trust Sanger Institute
• Allele ID: MGI:4346577
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Herc2^Gt(AR0530)Wtsi/Herc2^Gt(AR0530)Wtsi	involves: 129P2/OlaHsd * C57BL/6	MGI:6286196
ht2	Herc2^Gt(AR0530)Wtsi/Herc2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:6286198
cx3	Herc2^Gt(AR0530)Wtsi/Herc2^Gt(AR0530)Wtsi Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129P2/OlaHsd * C57BL/6	MGI:6286197

Genotype
MGI:6286196

hm1

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

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

mortality/aging

embryonic lethality, complete penetrance ( J:252045 )

• homozygous mutant embryos die before E7.5; some residuals are detected in placentas without embryos at E7.5 and E8.5, but these are completely resorbed by E10.5

Genotype
MGI:6286198

ht2

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

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

Genotype
MGI:6286197

cx3

• Allelic Composition: Herc2^{Gt(AR0530)Wtsi}/Herc2^{Gt(AR0530)Wtsi}; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

embryonic lethality, complete penetrance ( J:252045 )

• loss of Trp53 expression does not rescue the embryonic lethality of Herc2^{Gt(AR0530)Wtsi} homozygous mice