Phenotypes Associated with This Genotype

Genotype
MGI:5525137

• Allelic Composition: Tg(Wnk4*Q562E)#Rpl/Tg(Wnk4*Q562E)#Rpl
• Genetic Background: involves: C3H * C57BL/6

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

cardiovascular system

cardiovascular system phenotype ( J:113094 )

N • a high-salt (8%) diet increases blood pressure in mutants to a similar amount as in wild-type mice

N • a low-salt diet (0.1%) reduces blood pressure in mutants to a similar amount as in wild-type mice

increased systemic arterial diastolic blood pressure ( J:113094 )

• diastolic blood pressure is increased in 3-4 month old unanesthetized and unrestrained mutants

increased systemic arterial systolic blood pressure ( J:113094 )

• systolic blood pressure is increased in 3-4 month old unanesthetized and unrestrained mutants

homeostasis/metabolism

decreased circulating bicarbonate level ( J:113094 )

increased circulating magnesium level ( J:113094 )

hyperkalemia ( J:113094 )

• serum potassium is elevated

• on a 5% potassium diet, mutants survive, however they show an increase in serum potassium, but not urinary potassium levels, indicating a urinary secretory defect

• treatment with hydrochlorothiazide, a specific Slc12a3 inhibitor, corrects hyperkalemia

increased urine calcium level ( J:113094 )

• a 50% increase in urinary calcium

• the increase in urinary calcium is exacerbated on a high-salt diet, with mutants showing a 6-fold increase compared to a 2-fold increase in wild-type mice

• treatment with hydrochlorothiazide, a specific Slc12a3 inhibitor, corrects hypercalciuria

increased circulating chloride level ( J:113094 )

mortality/aging

premature death ( J:113094 )

• on a 10% potassium diet that is well tolerated by wild-type mice, mutants begin dying within several days

renal/urinary system

increased urine calcium level ( J:113094 )

• a 50% increase in urinary calcium

• the increase in urinary calcium is exacerbated on a high-salt diet, with mutants showing a 6-fold increase compared to a 2-fold increase in wild-type mice

• treatment with hydrochlorothiazide, a specific Slc12a3 inhibitor, corrects hypercalciuria

abnormal distal convoluted tubule morphology ( J:113094 )

• increase in apical surface area of distal convoluted tube epithelium

abnormal kidney physiology ( J:113094 )

• despite hyperkalemia, mutants show no increase in urinary potassium excretion, indicating impaired renal electrolyte handling

• on a 5% potassium diet, mutants survive, however they show an increase in serum potassium, but not urinary potassium levels, indicating a urinary secretory defect