Phenotypes Associated with This Genotype

Genotype
MGI:3611217

• Allelic Composition: Pdss2^kd/Pdss2^kd
• Genetic Background: CBA/H-Pdss2^kd

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

liver/biliary system

decreased hepatocyte mitochondrial DNA content ( J:197578 )

mortality/aging

premature death ( J:5232 )

• usually at 5 to 7 months

renal/urinary system

colorless urine ( J:5232 )

• urine became colorless as the animal aged

albuminuria ( J:5232 )

• increase in urinary protein at about 10 weeks of age

tubulointerstitial nephritis ( J:197578 )

• 6 month old, but not 4 month old, mutants show tubulointerstitial nephritis and collapsing glomerulopathy

abnormal kidney morphology ( J:197578 )

• kidney at 6 months of age shows tissue loss

kidney cyst ( J:5232 , J:197578 )

• cysts were seen only in kidneys with very advanced lesions (J:5232)

• microcystic formations (J:197578)

abnormal podocyte morphology ( J:197578 )

• podocyte damage is seen at 6 months of age

abnormal renal glomerulus morphology ( J:197578 )

• 6 month old mutants show collapsing glomerulopathy

glomerulosclerosis ( J:5232 , J:197578 )

• sclerotic in atrophied areas of the kidney (J:5232)

kidney atrophy ( J:5232 )

• at necropsy, kidneys appear contracted

renal tubule atrophy ( J:5232 )

• in the fully developed case in 4 to 6 months old mice, many of the tubules were atrophied in some places

dilated renal tubule ( J:5232 )

• a small number of tubules were distended with colloid casts at 10 to 14 weeks of age

• in the fully developed case in 4 to 6 months old mice, many of the tubules were dilated and atrophied in some places

renal cast ( J:5232 )

• a small number of tubules were distended with colloid casts at 10 to 14 weeks of age

granular kidney ( J:5232 )

• at necropsy

pale kidney ( J:5232 )

• at necropsy

behavior/neurological

polydipsia ( J:5232 )

• at 3 to 4 months of age

hunched posture ( J:5232 )

• mice become hunched at a few months of age

growth/size/body

weight loss ( J:5232 )

• at the age of 4-6 months

• progressively worse until death

kidney cyst ( J:5232 , J:197578 )

• cysts were seen only in kidneys with very advanced lesions (J:5232)

• microcystic formations (J:197578)

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:197578 )

• 1 month old mutants show CoQ9 levels that are 20% of controls in the brain, 28% in the kidney, 62% in the liver and 35% in the muscle

• 4 month old mutants show even further reduced levels of CoQ9, levels that are 16% of controls in the brain, 21% in the kidney, 25% in the muscle

• 6 month old mutants show CoQ9 levels that are 28% of controls in the brain, 14% in the kidney, 68% in the liver, and 20% in the muscle

• liver of 4 month old mutants has increased CoQ9; 157% of controls

colorless urine ( J:5232 )

• urine became colorless as the animal aged

albuminuria ( J:5232 )

• increase in urinary protein at about 10 weeks of age

cellular

decreased mitochondrial DNA content ( J:197578 )

• levels of mitochondrial DNA are decreased in the kidney (19%) at 4 months of age

• levels of mitochondrial DNA are decreased in the kidney (26%) and liver (71%) at 6 months of age

decreased hepatocyte mitochondrial DNA content ( J:197578 )

increased mitochondrial DNA content ( J:197578 )

• levels of mitochondrial DNA are increased in the brain (128%), and liver (120%) at 4 months of age

abnormal respiratory electron transport chain ( J:197578 )

• coenzyme Q (CoQ)-dependent complex I + III activity, normalized to citrate synthase activity, is reduced in the kidney at 4 and 6 months of age, and in the muscle at 6 months of age

• CoQ-dependent complex I + III activity, normalized to CS activity, is increased in the liver at 4 months of age, but not at 6 months

• CoQ-depended complex II + III activity, normalized to CS activity, is reduced in the kidney, brain, and liver, and slightly increased in the muscle of 1 month old mutants

• CoQ-depended complex II + III activity, normalized to CS activity, is reduced in the muscle at 6 months of age

• cytochrome c oxidase and citrate synthase activities are increased in the liver a 4 months of age

• citrate synthase activity is decreased in the kidney at 6 months of age

abnormal mitochondrial ATP synthesis coupled electron transport ( J:197578 )

• ATP concentration and ATP/ADP ratio are decreased in the kidney, slightly decreased in muscle, and slightly increased in the brain and liver at 4 months of age

• ATP levels and ATP/ADP ratio are decreased in the kidney and brain but are increased in the liver and muscle at 6 months of age

oxidative stress ( J:197578 )

• mutants show elevated reactive oxygen species (ROS) production in the kidney (at 1 and 4 months of age) and muscle (at 4 months of age, but not 6 months of age) following dihydroethidine injection compared to wild-type controls

• markers of oxidative stress are increased in sclerotic glomeruli, dilated tubuli, microcystic formations, and in some of the normal proximal and distal tubuli adjacent to affected areas at 6 months of age

immune system

tubulointerstitial nephritis ( J:197578 )

• 6 month old, but not 4 month old, mutants show tubulointerstitial nephritis and collapsing glomerulopathy

muscle

myopathy ( J:197578 )

• 4 and 6 month old mutants show variable muscle abnormalities, including central nuclei and fiber-type grouping and necrotic fibers

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
coenzyme Q10 deficiency disease		DOID:0050730	OMIM:PS607426	J:197578