Phenotypes Associated with This Genotype

Genotype
MGI:2449115

• Allelic Composition: Aprt^tm1Jat/Aprt^tm1Jat
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

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

mortality/aging

premature death ( J:33255 )

• 3X more prevalent in males than females

• Background Sensitivity: death in about 35% of mice on average around 75 days of age

growth/size/body

weight loss ( J:33255 )

• health deteriorates after weaning in the 35% of mice displaying weight loss

behavior/neurological

hunched posture ( J:33255 )

• Background Sensitivity: appears around 3-4 weeks of age

reproductive system

reduced fertility ( J:33255 )

• Background Sensitivity: involving both sexes in animals not overtly ill

homeostasis/metabolism

abnormal urine nucleoside level ( J:33255 )

• Background Sensitivity: detectable excretion of dihydroxyadenine primarily but also of adenine

decreased urine uric acid level ( J:33255 )

• uric acid excretion is about 50% of controls

renal/urinary system

abnormal urine nucleoside level ( J:33255 )

• Background Sensitivity: detectable excretion of dihydroxyadenine primarily but also of adenine

decreased urine uric acid level ( J:33255 )

• uric acid excretion is about 50% of controls

kidney inflammation ( J:33255 )

• 20-30% of kidney is inflamed at 6 weeks of age and 70-80% inflamed at 12 weeks

kidney collecting duct atrophy ( J:103956 )

♂ • at 3 months of age, atrophic cells are found in the collecting ducts of male mice

renal interstitial fibrosis ( J:33255 , J:103956 )

• very rapid progression of interstitial fibrosis (J:33255)

• renal interstitial fibrosis is seen in both the male and female kidneys, with males exhibiting much greater change at 3 months of age (J:103956)

• significant renal pathology is noted in kidneys of male mice with very high levels of stone material (J:103956)

renal tubule atrophy ( J:103956 )

• at 3 months of age, atrophic cells are seen primarily in the S3 segment of proximal tubules as well as in the distal tubules of male mice

nephrolithiasis ( J:103956 )

• at 1-2 days of age, DHA crystals are found within the lumens of cortical and medullary collecting ducts of both male and female mice

• by 2 weeks of age, DHA crystals are detected in the lumens of proximal and distal tubules as well as collecting ducts

• crystals are brownish red in color, generally spherical (~10-20 um in diameter), and display numerous slender needle- to lancet-shaped structures radiating from the center of the crystal

• DHA crystals are also found within areas of interstitial fibrosis, surrounding atrophic cells of the S3 segment of the proximal tubule, as well as atrophic cells of the distal tubule and collecting ducts

• DHA crystals surrounding the atrophic tubular segments are not spherical but composed of numerous slender rod- to needle-shaped structures

• crystals are birefringent under polarizing optics regardless of their location

• tissue staining and fixation procedures drastically reduces the amount of birefringent material

• occasionally, several crystals aggregate within the tubular lumen, forming a much larger stone

• crystal formation is significantly greater in 120- to 240-day-old males relative to age-matched females

cystolithiasis ( J:33255 , J:103956 )

• Background Sensitivity: urinary crystals and stones in the bladder are composed of dihydroxyadenine (J:33255)

• at 3 months of age, individual DHA crystals are seen in an aggregated DHA stone in the urinary bladder of male mice (J:103956)

• crystals are spherical in shape and composed of numerous needle-shaped substructures and of 6-amino-2,8(3,9)-purine dione (a tautomeric form of DHA) (J:103956)

immune system

kidney inflammation ( J:33255 )

• 20-30% of kidney is inflamed at 6 weeks of age and 70-80% inflamed at 12 weeks

integument

disheveled coat ( J:33255 )

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

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