Analysis Tools
craniofacial
 |
• at 8 weeks, a small number of mutants exhibit backward growth of the teeth
• feeding a liquid diet results in long-term survival but does not improve the teeth or humpback deformities
|
homeostasis/metabolism
aminoaciduria
(
J:66560
)
|
|
• hemizygotes show generalized aminoaciduria
• hyperaminoaciduria is more pronounced for neutral and polar amino acids, e.g. citrulline (94-fold increase), hydroxyproline (24-fold increase), cysteine (22-fold increase), glutamine (11-fold increase) and threonine (10-fold increase)
• in contrast, plasma levels of amino acids remain unaffected relative to wild-type
|
|
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• 24-fold increase in urine hydroxyproline level
|
cystinuria
(
J:66560
)
|
|
• 22-fold increase in urine cysteine levels
|
|
|
• 11-fold increase in urine glutamine levels
|
|
|
• 10-fold increase in urine threonine levels
|
|
|
• hemizygotes exhibit significant glycosuria that is not associated with hyperglycemia
|
|
|
• hemizygotes display a 2-fold increase in daily urinary excretion of calcium relative to wild-type
|
|
|
• hemizygotes display a severe impairment of protein endocytosis by the kidney proximal tubule cells (PTCs)
(J:66560)
• analytical subcellular fractionation and quantitative immunogold labeling revealed that impaired apical protein endocytosis is due to a trafficking defect of megalin and cubilin in PTCs
(J:84433)
• failure of apical endocytosis ocucrs in the absence of ultrastructural changes in PTCs or deficits in rate-limiting endocytic catalysts
(J:84433)
|
|
|
• hemizygotes show a low molecular weight proteinuria that includes vitamin D binding protein (DBP, 50 kDa) and Clara cell protein (CC16, 16 kDa)
• specifically, hemizygotes show a 200-fold increase in urinary CC16 excretion relative to wild-type; in contrast, plasma CC16 concentrations remain normal
|
renal/urinary system
|
N |
• hemizygotes display normal kidney clearance, as assessed by plasma creatinine and creatinine clearance standardized for body weight
|
aminoaciduria
(
J:66560
)
|
|
• hemizygotes show generalized aminoaciduria
• hyperaminoaciduria is more pronounced for neutral and polar amino acids, e.g. citrulline (94-fold increase), hydroxyproline (24-fold increase), cysteine (22-fold increase), glutamine (11-fold increase) and threonine (10-fold increase)
• in contrast, plasma levels of amino acids remain unaffected relative to wild-type
|
|
|
• 24-fold increase in urine hydroxyproline level
|
cystinuria
(
J:66560
)
|
|
• 22-fold increase in urine cysteine levels
|
|
|
• 11-fold increase in urine glutamine levels
|
|
|
• 10-fold increase in urine threonine levels
|
|
|
• hemizygotes exhibit significant glycosuria that is not associated with hyperglycemia
|
|
|
• hemizygotes display a 2-fold increase in daily urinary excretion of calcium relative to wild-type
|
|
|
• hemizygotes display a severe impairment of protein endocytosis by the kidney proximal tubule cells (PTCs)
(J:66560)
• analytical subcellular fractionation and quantitative immunogold labeling revealed that impaired apical protein endocytosis is due to a trafficking defect of megalin and cubilin in PTCs
(J:84433)
• failure of apical endocytosis ocucrs in the absence of ultrastructural changes in PTCs or deficits in rate-limiting endocytic catalysts
(J:84433)
|
|
|
• hemizygotes show a low molecular weight proteinuria that includes vitamin D binding protein (DBP, 50 kDa) and Clara cell protein (CC16, 16 kDa)
• specifically, hemizygotes show a 200-fold increase in urinary CC16 excretion relative to wild-type; in contrast, plasma CC16 concentrations remain normal
|
|
|
• mutant kidneys exhibit microscopic calcium deposits at the cortico-medullary junction
|
|
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• mutant kidneys appear histologically normal but exhibit microscopic calcium deposits at the cortico-medullary junction, indicating nephrocalcinosis
|
|
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• in some hemizygotes, the polyuria, which correlates with glycosuria, results in a daily diuresis that is 50% greater than that in wild-type littermates and is equivalent to 30% of body weight
|
skeleton
|
|
• at 8 weeks, a small number of mutants exhibit backward growth of the teeth
• feeding a liquid diet results in long-term survival but does not improve the teeth or humpback deformities
|
|
|
• most mutants are viable at birth and display normal growth and survival to reproductive age
• however, at 8 weeks, ~7% of mutants show hump deformities of the dorsal spine, in the absence of osteopenia or rickets
|
growth/size/body
|
|
• at 8 weeks, a small number of mutants exhibit backward growth of the teeth
• feeding a liquid diet results in long-term survival but does not improve the teeth or humpback deformities
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Dent disease | DOID:0050699 |
OMIM:300009 OMIM:300555 |
J:66560 | |
