Mouse Genome Informatics
hm
    Uoxtm1Bay/Uoxtm1Bay
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Pathology of urate neophropathy in Uoxtm1Bay/Uoxtm1Bay mice

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)
• crystals appear rapidly as urine cools
• kidneys exhibit cortical foci of fibrosis

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)
• 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)
• kidneys exhibit cortical foci of fibrosis
• 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)
• 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
• exhibit mechanical blockage of renal tubules by urate crystal deposition within tubular lumens
• 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
• as disease progresses, affected kidneys become discolored (pale yellow)
• bladders of some adults are dilated and contain uric acid stones
• in some adults
• exhibit about 6-fold more urine output

immune system
• chronic inflammation, characterized by infiltration of plasma cells, lymphocytes, and macrophages, occurs within the interstitium of the kidney

behavior/neurological
• ingest about 5-fold more water

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Insipidus, Nephrogenic, Autosomal 125800 J:103187