Phenotypes associated with this allele

• Allele Symbol: Cldn8^tm1.1Jhou
• Allele Name: targeted mutation 1.1, Jianghui Hou
• Allele ID: MGI:5750892
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cldn8^tm1.1Jhou/Cldn8^tm1.1Jhou Tg(Aqp2-cre)1Dek/0	B6.Cg-Cldn8^tm1.1Jhou Tg(Aqp2-cre)1Dek	MGI:5803713

Genotype
MGI:5803713

cn1

• Allelic Composition: Cldn8^tm1.1Jhou/Cldn8^tm1.1Jhou; Tg(Aqp2-cre)1Dek/0
• Genetic Background: B6.Cg-Cldn8^tm1.1Jhou Tg(Aqp2-cre)1Dek

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

Delocalization of claudin-4 in the tight junction of Cldn8^tm1.1Jhou/Cldn8^tm1.1Jhou Tg(Aqp2-cre)1Dek/0 kidney collecting duct

homeostasis/metabolism

increased circulating bicarbonate level ( J:220813 )

• significantly increased arterial HCO3^- level (P_HCO3) at 10-12 weeks of age

• however, arterial pH is normal

increased circulating aldosterone level ( J:220813 )

• plasma aldosterone level is significantly increased by 1.48-fold relative to controls

decreased circulating potassium level ( J:220813 )

• significantly reduced plasma K⁺ level (P_K) at 10-12 weeks of age, indicating hypokalemia

hypokalemia ( J:220813 )

decreased circulating chloride level ( J:220813 )

• significantly reduced plasma Cl^- level (P_Cl) at 10-12 weeks of age

• however, plasma Na⁺ level (P_Na) is normal

increased urine chloride ion level ( J:220813 )

• significantly increased urinary Cl^- excretion rates, with fractional excretion increased by 1.72-fold and absolute excretion increased by 1.67-fold relative to controls

increased urine potassium level ( J:220813 )

• significant renal wasting of K⁺, with fractional excretion increased by 1.75-fold and absolute excretion increased by 1.67-fold relative to controls

increased urine sodium level ( J:220813 )

• significantly increased urinary Na⁺ excretion rates, with fractional excretion increased by 1.49-fold and absolute excretion increased by 1.51-fold relative to controls

alkalosis ( J:220813 )

• metabolic alkalosis due renal loss of Cl^- at 10-12 weeks of age

renal/urinary system

increased urine chloride ion level ( J:220813 )

• significantly increased urinary Cl^- excretion rates, with fractional excretion increased by 1.72-fold and absolute excretion increased by 1.67-fold relative to controls

increased urine potassium level ( J:220813 )

• significant renal wasting of K⁺, with fractional excretion increased by 1.75-fold and absolute excretion increased by 1.67-fold relative to controls

increased urine sodium level ( J:220813 )

• significantly increased urinary Na⁺ excretion rates, with fractional excretion increased by 1.49-fold and absolute excretion increased by 1.51-fold relative to controls

abnormal kidney collecting duct morphology ( J:220813 )

• mice show delocalization of claudin-4 from the tight junction (TJ) in the collecting duct relative to control mice

• however, collecting duct histology, barrier function and TJ integrity remain intact

polyuria ( J:220813 )

• significant increase in urinary volume at 10-12 weeks of age relative to control mice

• however, urinary osmotic pressure is normal

cardiovascular system

decreased mean systemic arterial blood pressure ( J:220813 )

• mean arterial blood pressure (BP) in anesthetized mice is 17.6 mmHg lower than in control mice

• in vivo telemetric recording showed that the mean BP of awake and unrestrained males is consistently lower than in control males throughout the 24-h period, with statistical significance reached for each time point

hypotension ( J:220813 )

• hypotension associated with renal salt wasting defects and urinary volume depletion

growth/size/body

growth/size/body region phenotype ( J:220813 )

N • at 10-12 weeks of age, mice fed a regular salt diet show normal body weight relative to controls