Phenotypes associated with this allele

• Allele Symbol: Aprt^tm1Jat
• Allele Name: targeted mutation 1, Jay A Tischfield
• Allele ID: MGI:1857278
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Aprt^tm1Jat/Aprt^tm1Jat	involves: 129S2/SvPas * Black Swiss	MGI:2449114
hm2	Aprt^tm1Jat/Aprt^tm1Jat	involves: 129S2/SvPas * C57BL/6J	MGI:2449115
ht3	Aprt^tm1Jat/Aprt^+	involves: 129S2/SvPas * C57BL/6J	MGI:5432779
cx4	Aprt^tm1Jat/Aprt^tm1Jat Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S2/SvPas * 129S7/SvEvBrd	MGI:4361876

Genotype
MGI:2449114

hm1

• 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

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)

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

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

cellular

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)

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

Genotype
MGI:2449115

hm2

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

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

Genotype
MGI:5432779

ht3

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

renal/urinary system

nephrolithiasis ( J:103956 )

• some heterozygotes display crystalline material in the renal pelvis at autopsy

• a small amount of DHA crystal material is found in kidneys of both sexes, with no significant difference between male and female mice at 7-14 or at 30-45 days of age

• however, no renal pathological changes are observed at any age

Genotype
MGI:4361876

cx4

• Allelic Composition: Aprt^tm1Jat/Aprt^tm1Jat; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd

mortality/aging

postnatal lethality ( J:114314 )

• fewer than expected female pups are observed (no time point of death given)

renal/urinary system

abnormal urine nucleoside level ( J:114314 )

• at 12 weeks, purine excretion in male mice is higher than in Aprt^tm1Jat homozygotes

abnormal kidney morphology ( J:114314 )

• at 12 weeks, female mice exhibit a more severe renal pathology than Aprt^tm1Jat homozygotes

growth/size/body

abnormal body weight ( J:114314 )

• growth curve analysis indicates that female mice are smaller at young ages but exhibit rapid weight gain in order to achieve normal maximal weight

decreased body weight ( J:114314 )

• in male mice compared with Aprt^tm1Jat homozygotes

homeostasis/metabolism

abnormal urine nucleoside level ( J:114314 )

• at 12 weeks, purine excretion in male mice is higher than in Aprt^tm1Jat homozygotes