Phenotypes Associated with This Genotype

Genotype
MGI:2449114

• Allelic Composition: Aprt^tm1Jat/Aprt^tm1Jat
• Genetic Background: involves: 129S2/SvPas * Black Swiss

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

Kidney histopathology of a Aprt^tm1Jat/Aprt^tmiJat mouse

mortality/aging

premature death ( J:33255 )

• Background Sensitivity: death on average around 180 days of age for about 35% of mice

• 3X more prevalent in males than in females

growth/size/body

weight loss ( J:33255 , J:111451 )

• health deteriorates after weaning in the 35% of mice showing weight loss (J:33255)

behavior/neurological

increased fluid intake ( J:111451 )

♂ • higher water intake in males

hunched posture ( J:33255 )

• appears around 3-4 months of age

reproductive system

reproductive system phenotype ( J:33255 )

N • Background Sensitivity: fertility is normal on this background

homeostasis/metabolism

increased blood urea nitrogen level ( J:111451 )

• elevated blood urea nitrogen levels which improve at later ages, probably due to the death of more severely affected mice

abnormal urine nucleoside level ( J:33255 )

• Background Sensitivity: excretion primarily of adenine which is more soluble than dihydroxyadenine

decreased urine uric acid level ( J:33255 )

• uric acid excretion is about 50% of controls

crystalluria ( J:111451 )

• excretion of crystals in urine as early as 40 weeks in 50% of mice

renal/urinary system

abnormal urine nucleoside level ( J:33255 )

• Background Sensitivity: excretion primarily of adenine which is more soluble than dihydroxyadenine

decreased urine uric acid level ( J:33255 )

• uric acid excretion is about 50% of controls

crystalluria ( J:111451 )

• excretion of crystals in urine as early as 40 weeks in 50% of mice

kidney inflammation ( J:33255 )

• mild to moderate kidney inflammation at 4 weeks of age

• severe parenchymal damage by 8-24 weeks

• as much as 50-80% of kidneys may exhibit severe inflammation and fibrosis

decreased kidney weight ( J:111451 )

♂ • in 12 week old males

kidney atrophy ( J:111451 )

• in 85% at 12 weeks of age including collase of tubules

• damage much more severe in males than females

dilated renal tubule ( J:33255 )

• 10-20% of tubules are dilated but glomeruli are generally normal

• tubule dilation as early as 4 weeks of age

renal tubular necrosis ( J:33255 , J:111451 )

• rays of tubular necrosis and regeneration surrounding areas of crystal formation (J:33255)

• necrosis and fibrosis as early as 4 weeks of age (J:111451)

nephrolithiasis ( J:33255 , J:111451 )

• intracellular and intratubular crystal formation (J:33255)

• crystals and stones increase with age (J:33255)

• crystal formation much more severe in males (J:111451)

renal fibrosis ( J:33255 )

• as much as 50-80% of kidneys may exhibit severe inflammation and fibrosis

cystolithiasis ( J:33255 )

• urinary crystals and stones in the bladder are composed of dihydroxyadenine

decreased creatinine clearance ( J:111451 )

♂ • 51% of normal in males

polyuria ( J:111451 )

♂ • increased urine excretion in males

hematopoietic system

decreased hematocrit ( J:111451 )

♂ • in 12 week old males

immune system

kidney inflammation ( J:33255 )

• mild to moderate kidney inflammation at 4 weeks of age

• severe parenchymal damage by 8-24 weeks

• as much as 50-80% of kidneys may exhibit severe inflammation and fibrosis

integument

disheveled coat ( J:33255 )

• Background Sensitivity: symptoms appear around 3-4 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adenine phosphoribosyltransferase deficiency		DOID:0060350	OMIM:614723	J:33255