Mouse Genome Informatics
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    Atp6v0a4tm1.1Fekf/Atp6v0a4tm1.1Fekf
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Small size and hydronephrotic kidney in Atp6v0a4tm1.1Fekf/Atp6v0a4tm1.1Fekf mice

mortality/aging
• vast majority die around the time of weaning
• providing damns and pups with alkalinized water improves survival
• almost no untreated mice survive longer than 6 months
• providing damns and pups with alkalinized water improves survival
• some mice fail to thrive, rapidly lose weight and die or have to be killed within 14 days of alkali withdrawal but most survive if alkali is withdrawn at ages varying from 5 weeks to 2.5 months

homeostasis/metabolism
N
• unlike in humans with distal renal tubular acidosis, serum and urinary calcium levels are similar to controls (J:188593)
• providing damns and pups with alkalinized water increases Potassium levels
• indicated by elevated urea and osmolality and despite normal excretory renal function
• providing damns and pups with alkalinized water decreases dehydration
• marked spontaneous hyperchloremic non?anion gap acidosis in unweaned mice
• providing damns and pups with alkalinized water decreases acidosis
• hypocitraturia in adults after withdrawal of alkali treatment
• at P21 and in adults after withdrawal of alkali treatment

renal/urinary system
• hypocitraturia in adults after withdrawal of alkali treatment
• at P21 and in adults after withdrawal of alkali treatment
• unilateral in 2 of 3 long term survivors and severe bilateral in the third
• unilateral hydronephrosis in 1 of 71 at 15 days of age
• detected in 20% of alkalinized mice
• tubular vacuolation is seen at P14 and P21
• lifelong alkalinization rescues vacuolation but vacuoles often develop after treatment withdrawal
• mild in 7 of 18 kidneys from weanlings
• one of three long term survivors had marked medullary nephrocalcinosis
• in 1 mouse, composed of struvite
• in mice that receive alkali treatment

hearing/vestibular/ear
• lack visible otoconial crystal
• no measurable ABRs were evoked by click stimuli
• large elevations in ABR thresholds are seen for all frequencies from 3?42 kHz at P20
• severely impaired hearing

taste/olfaction
• fail to show a preference for urine from a nonfamiliar animal of the opposite sex over water

growth/size/body
• at 2 - 3 weeks of age
• at 2 - 3 weeks of age
• providing damns and pups with alkalinized water rescues the decrease in body weight

behavior/neurological
• in mice that receive alkali treatment
• fail to show a preference for urine from a nonfamiliar animal of the opposite sex over water in an olfactory discrimination assay

Mouse Models of Human Disease
OMIM IDRef(s)
Renal Tubular Acidosis, Distal, Autosomal Recessive; RTADR 602722 J:188593