Phenotypes Associated with This Genotype

Genotype
MGI:5642335

• Allelic Composition: Atp13a2^tm1.2Wtd/Atp13a2^tm1.2Wtd
• Genetic Background: involves: 129 * C57BL/6

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

behavior/neurological

limb grasping ( J:221680 )

• 18 month old mice clasp their rear limbs during tail suspension

decreased locomotor activity ( J:221680 )

• mice show decreased spontaneous horizontal movement in the open field

• however, 18 month old mice show normal rotarod performance and rearing behavior

homeostasis/metabolism

impaired autophagy ( J:221680 )

• mice show selective defects in autophagy function

nervous system

gliosis ( J:221680 )

• brains exhibit an increase in gliosis throughout many brain regions, including, but not limited to, cortex, striatum, hippocampus, cerebellum, thalamus, and midbrain, at 18 months of age

• gliosis in the cortex is seen as early as 1 month of age which increases with age

astrocytosis ( J:221680 )

abnormal neuron morphology ( J:221680 )

• mice exhibit large ubiquitin-positive protein aggregates by 12 months of age, most prominent in the cortex and hippocampus; inclusions localize within neurons

• neurons accumulate lipid droplets which are larger and more numerous than in controls and are associated with lipofuscin

• however, no alpha-synuclein abnormalities are seen and no ubiquitin- or alpha-synuclein-positive aggregates are seen in dopaminergic cells and mice exhibit normal numbers of dopaminergic neurons

pigmentation

lipofuscinosis ( J:221680 )

• mice exhibit increased lipofuscinosis in multiple brain regions at 3 months of age

• lipofuscin deposits consist of large, electron dense material, frequently containing membranous structures, in close association with large lipid droplets

cellular

abnormal lysosome morphology ( J:221680 )

• age-dependent accumulation of lysosomal proteins and lipids lysosomal accumulation in multiple brain regions

impaired autophagy ( J:221680 )

• mice show selective defects in autophagy function

abnormal lysosome physiology ( J:221680 )

• endolysosomal pathway dysfunction characterized by decreased cathepsin D processing and decreased clearance of autophagic substrates, however lysosomal function appears normal

lysosomal protein accumulation ( J:221680 )

• accumulation of lysosomal proteins by 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Kufor-Rakeb syndrome		DOID:0060556	OMIM:606693	J:221680