Mouse Genome Informatics
hm1
    Aprttm1Jat/Aprttm1Jat
involves: 129S2/SvPas * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Kidney histopathology of a Aprttm1Jat/AprttmiJat mouse

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

behavior/neurological
• higher water intake in males (J:111451)
• appears around 3-4 months of age

reproductive system
N
• Background Sensitivity: fertility is normal on this background (J:33255)

homeostasis/metabolism
• elevated blood urea nitrogen levels which improve at later ages, probably due to the death of more severely affected mice
• Background Sensitivity: excretion primarily of adenine which is more soluble than dihydroxyadenine
• uric acid excretion is about 50% of controls
• excretion of crystals in urine as early as 40 weeks in 50% of mice
• as much as 50-80% of kidneys may exhibit severe inflammation and fibrosis

renal/urinary system
• Background Sensitivity: excretion primarily of adenine which is more soluble than dihydroxyadenine
• uric acid excretion is about 50% of controls
• excretion of crystals in urine as early as 40 weeks in 50% of mice
• as much as 50-80% of kidneys may exhibit severe inflammation and fibrosis
• 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
• in 12 week old males (J:111451)
• in 85% at 12 weeks of age including collase of tubules
• damage much more severe in males than females
• 10-20% of tubules are dilated but glomeruli are generally normal
• tubule dilation as early as 4 weeks of age
• 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)
• intracellular and intratubular crystal formation (J:33255)
• crystals and stones increase with age (J:33255)
• crystal formation much more severe in males (J:111451)
• urinary crystals and stones in the bladder are composed of dihydroxyadenine
• 51% of normal in males (J:111451)
• increased urine excretion in males (J:111451)

hematopoietic system
• in 12 week old males (J:111451)

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

Mouse Models of Human Disease
OMIM IDRef(s)
Adenine Phosphoribosyltransferase Deficiency; APRTD 614723 J:33255


Mouse Genome Informatics
hm2
    Aprttm1Jat/Aprttm1Jat
involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 3X more prevalent in males than females
• Background Sensitivity: death in about 35% of mice on average around 75 days of age

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

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

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

homeostasis/metabolism
• Background Sensitivity: detectable excretion of dihydroxyadenine primarily but also of adenine
• uric acid excretion is about 50% of controls
• 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/urinary system
• Background Sensitivity: detectable excretion of dihydroxyadenine primarily but also of adenine
• uric acid excretion is about 50% of controls
• 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)
• 20-30% of kidney is inflamed at 6 weeks of age and 70-80% inflamed at 12 weeks
• at 3 months of age, atrophic cells are found in the collecting ducts of male mice (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
• 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
• 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
• 20-30% of kidney is inflamed at 6 weeks of age and 70-80% inflamed at 12 weeks

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

Mouse Models of Human Disease
OMIM IDRef(s)
Adenine Phosphoribosyltransferase Deficiency; APRTD 614723 J:33255


Mouse Genome Informatics
ht3
    Aprttm1Jat/Aprt+
involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• 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


Mouse Genome Informatics
cx4
    Aprttm1Jat/Aprttm1Jat
Spp1tm1Rit/Spp1tm1Rit

involves: 129S2/SvPas * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected female pups are observed (no time point of death given)

renal/urinary system
• at 12 weeks, purine excretion in male mice is higher than in Aprttm1Jat homozygotes
• at 12 weeks, female mice exhibit a more severe renal pathology than Aprttm1Jat homozygotes

growth/size
• growth curve analysis indicates that female mice are smaller at young ages but exhibit rapid weight gain in order to achieve normal maximal weight
• in male mice compared with Aprttm1Jat homozygotes

homeostasis/metabolism
• at 12 weeks, purine excretion in male mice is higher than in Aprttm1Jat homozygotes