Mouse Genome Informatics
ot
    Clcn5tm1Tjj/Y
B6.129-Clcn5tm1Tjj
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
homeostasis/metabolism
• mutant urine is slightly acidic relative to wild-type (J:77111)
• urinary phosphate excretion is increased by about 50% (J:77111)
• however, no hypercalciuria is observed (J:77111)
• mutants exhibit low-molecular-weight proteinuria (J:77111)
• vitamin D binding protein and retinol binding protein are highly elevated in the urine of mutant mice (J:77111)
• iodinated beta-2 microglobulin is lost into the urine in much larger quantities relative to wild-type (J:77111)
• mutants display upregulation of proximal tubular alpha-hydroxylation of 25(OH) vitamin D3 to the active hormone (J:91340)

liver/biliary system
N
• mutant mice display no significant defect in endocytosis of asialofetuin in the liver (J:77111)

renal/urinary system
N
• mutant kidneys appear morphologically and histologically normal (J:77111)
• no kidney stones or nephrocalcinosis are observed even after one year (J:77111)
• mutant urine is slightly acidic relative to wild-type (J:77111)
• urinary phosphate excretion is increased by about 50% (J:77111)
• however, no hypercalciuria is observed (J:77111)
• mutants exhibit low-molecular-weight proteinuria (J:77111)
• vitamin D binding protein and retinol binding protein are highly elevated in the urine of mutant mice (J:77111)
• iodinated beta-2 microglobulin is lost into the urine in much larger quantities relative to wild-type (J:77111)
• mutant kidneys show impaired apical proximal tubular endocytosis (J:77111)
• in autoradiography studies, radioactivity accumulates in deeper (probably pelvic) regions of mutant kidneys as opposed to the cortical region (i.e. proximal tubules) (J:77111)
• following injection of fluorescently labelled lactoglobulin, wild-type mice accumulate substantial amounts of the protein in vesicles below the brush border of PT cells; in contrast, mutant tubules take up much less protein (J:77111)
• endocytosis of horseradish peroxidase and of FITC-dextran is also inhibited (J:77111)
• internalization of the apical transporters NaPi-2 and NHE3 is retarded; at steady state, however, both proteins are redistributed from the plasma membrane to intracellular vesicles (J:77111)
• defective tubular endocytosis results in increased luminal concentration of parathyroid hormone (PTH) and subsequent stimulation of apical PTH receptors (J:91340)
• in mutants, apical endosomes of proximal tubular cells are acidified at a significantly lower rate relative to wild-type endosomes (J:91340)
• mutant mice produce slightly more urine (J:77111)

Mouse Models of Human Disease
OMIM IDRef(s)
Dent Disease 1 300009 J:77111