Phenotypes Associated with This Genotype

Genotype
MGI:3046533

• Allelic Composition: Clcn5^tm1Tjj/Y
• Genetic Background: B6.129-Clcn5^tm1Tjj

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

decreased urine pH ( J:77111 )

♂ • mutant urine is slightly acidic relative to wild-type

increased urine phosphate level ( J:77111 )

♂ • urinary phosphate excretion is increased by about 50%

♂ • however, no hypercalciuria is observed

increased urine protein level ( J:77111 )

♂ • mutants exhibit low-molecular-weight proteinuria

♂ • vitamin D binding protein and retinol binding protein are highly elevated in the urine of mutant mice

increased urine beta2-microglobulin level ( J:77111 )

♂ • iodinated beta-2 microglobulin is lost into the urine in much larger quantities relative to wild-type

abnormal metabolism ( J:91340 )

♂ • mutants display upregulation of proximal tubular alpha-hydroxylation of 25(OH) vitamin D3 to the active hormone

liver/biliary system

liver/biliary system phenotype ( J:77111 )

♂N • mutant mice display no significant defect in endocytosis of asialofetuin in the liver

renal/urinary system

renal/urinary system phenotype ( J:77111 )

♂N • mutant kidneys appear morphologically and histologically normal

♂N • no kidney stones or nephrocalcinosis are observed even after one year

decreased urine pH ( J:77111 )

♂ • mutant urine is slightly acidic relative to wild-type

increased urine phosphate level ( J:77111 )

♂ • urinary phosphate excretion is increased by about 50%

♂ • however, no hypercalciuria is observed

increased urine protein level ( J:77111 )

♂ • mutants exhibit low-molecular-weight proteinuria

♂ • vitamin D binding protein and retinol binding protein are highly elevated in the urine of mutant mice

increased urine beta2-microglobulin level ( J:77111 )

♂ • iodinated beta-2 microglobulin is lost into the urine in much larger quantities relative to wild-type

abnormal renal transport ( J:77111 , J:91340 )

♂ • 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)

polyuria ( J:77111 )

♂ • mutant mice produce slightly more urine

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Dent disease		DOID:0050699	OMIM:300009 OMIM:300555	J:77111