mortality/aging
• Background Sensitivity: 65% die within 4 weeks of age on the mixed 129S7/SvEvBrd and C57BL/6J background while a higher rate of lethality is seen on a 129/Sv background
|
homeostasis/metabolism
• develop hyperuricemia, with 10-fold higher levels of serum uric acid levels
|
• exhibit moderate azotemia, however do not observe signs of renal insufficiency
|
• serum urea nitrogen concentrations at 50-60 days and 9-13 months of age are 1.5- and 2-fold, respectively, higher than in controls
|
• mutants as young as 10 to 12 days of age produce copious pale urine
|
• urine osmolality is much lower than in controls
• ability to concentrate urine when deprived of water is severely impaired
|
• develop hyperuricosuria (10x more urinary uric acid than normal)
(J:16490)
• uric acid/creatine molar ratio in the urine is 30- to 100-fold higher
(J:103187)
|
crystalluria
(
J:103187
)
• crystals appear rapidly as urine cools
|
renal/urinary system
• mutants as young as 10 to 12 days of age produce copious pale urine
|
• urine osmolality is much lower than in controls
• ability to concentrate urine when deprived of water is severely impaired
|
• develop hyperuricosuria (10x more urinary uric acid than normal)
(J:16490)
• uric acid/creatine molar ratio in the urine is 30- to 100-fold higher
(J:103187)
|
crystalluria
(
J:103187
)
• crystals appear rapidly as urine cools
|
• chronic inflammation, characterized by infiltration of plasma cells, lymphocytes, and macrophages, occurs within the interstitium of the kidney
|
• exhibit progressive destruction of the kidneys as early as 6 days after birth, showing small cortical cysts and white-yellow deposits (urate crystals) which persist until P14 and then gradually resolve
(J:16490)
• as disease progresses, affected kidneys become smaller, discolored (pale yellow) and soft
(J:16490)
|
kidney cyst
(
J:16490
)
• the surface of the kidney becomes irregular with obvious pits and scars and multiple cysts
|
• cortical cysts start as dilations within the collecting tubules and extend from the papilla to the corticomedullary junction
|
• in both the cortex and medulla, collecting ducts are markedly dilated
|
• as obstructive disease progresses, hydronephrotic lesions appear and result in hydronephrosis at 5 weeks
(J:16490)
• exhibit scarred, irregularly shaped, hydronephrotic kidneys
(J:103187)
|
small kidney
(
J:16490
)
• as disease progresses, affected kidneys become smaller
|
• glomeruli are associated with foci of tubular atrophy and collapse of the nephron
|
• dilation of Bowman's spaces
|
• kidneys exhibit tubular atrophy with apparent crowding of glomeruli
|
• tubular degeneration and regeneration with dilation of tubules are seen at P8
• exhibit mechanical blockage of renal tubules by urate crystal deposition within tubular lumens
|
• kidneys exhibit tubular atrophy
|
• dilation of tubules at P8
|
renal cast
(
J:16490
)
• exhibit mechanical blockage of renal tubules by urate crystal deposition within tubular lumens
|
pale kidney
(
J:16490
)
• as disease progresses, affected kidneys become discolored (pale yellow)
|
• kidneys exhibit cortical foci of fibrosis
|
• bladders of some adults are dilated and contain uric acid stones
|
• in some adults
|
immune system
• chronic inflammation, characterized by infiltration of plasma cells, lymphocytes, and macrophages, occurs within the interstitium of the kidney
|
behavior/neurological
polydipsia
(
J:103187
)
• ingest about 5-fold more water
|
growth/size/body
kidney cyst
(
J:16490
)
• the surface of the kidney becomes irregular with obvious pits and scars and multiple cysts
|
• cortical cysts start as dilations within the collecting tubules and extend from the papilla to the corticomedullary junction
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
hyperuricemia | DOID:1920 | J:16490 | ||
nephrogenic diabetes insipidus | DOID:12387 | J:103187 |