Phenotypes Associated with This Genotype

Genotype
MGI:5441585

• Allelic Composition: Atp6v0a4^tm1.1Fekf/Atp6v0a4^tm1.1Fekf
• Genetic Background: involves: C57BL/6

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

Small size and hydronephrotic kidney in Atp6v0a4^tm1.1Fekf/Atp6v0a4^tm1.1Fekf mice

mortality/aging

premature death ( J:188593 )

• 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rapidly lose weight and die or have to be killed within 14 days of alkali withdrawal but most survive if alkali is withdrawn at ages varying from 5 weeks to 2.5 months

postnatal lethality, incomplete penetrance ( J:188593 )

• vast majority die around the time of weaning

• providing damns and pups with alkalinized water improves survival

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:188593 )

N • unlike in humans with distal renal tubular acidosis, serum and urinary calcium levels are similar to controls

increased blood osmolality ( J:188593 )

increased blood urea nitrogen level ( J:188593 )

hypokalemia ( J:188593 )

• providing damns and pups with alkalinized water increases Potassium levels

dehydration ( J:188593 )

• indicated by elevated urea and osmolality and despite normal excretory renal function

• providing damns and pups with alkalinized water decreases dehydration

increased circulating chloride level ( J:188593 )

acidosis ( J:188593 )

• marked spontaneous hyperchloremic non-anion gap acidosis in unweaned mice

• providing damns and pups with alkalinized water decreases acidosis

abnormal urine homeostasis ( J:188593 )

• hypocitraturia in adults after withdrawal of alkali treatment

decreased urine pH ( J:188593 )

• at P21 and in adults after withdrawal of alkali treatment

renal/urinary system

abnormal urine homeostasis ( J:188593 )

• hypocitraturia in adults after withdrawal of alkali treatment

decreased urine pH ( J:188593 )

• at P21 and in adults after withdrawal of alkali treatment

hydronephrosis ( J:188593 )

• 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

abnormal renal tubule morphology ( J:188593 )

• tubular vacuolation is seen at P14 and P21

• lifelong alkalinization rescues vacuolation but vacuoles often develop after treatment withdrawal

nephrocalcinosis ( J:188593 )

• mild in 7 of 18 kidneys from weanlings

• one of three long term survivors had marked medullary nephrocalcinosis

cystolithiasis ( J:188593 )

• in 1 mouse, composed of struvite

polyuria ( J:188593 )

• in mice that receive alkali treatment

hearing/vestibular/ear

abnormal inner ear morphology ( J:188593 )

dilated scala media ( J:188593 )

dilated endolymphatic duct ( J:188593 )

absent otoliths ( J:188593 )

• lack visible otoconial crystal

absent endocochlear potential ( J:188593 )

increased or absent threshold for auditory brainstem response ( J:188593 )

• no measurable ABRs were evoked by click stimuli

• large elevations in ABR thresholds are seen for all frequencies from 3?42 kHz at P20

impaired hearing ( J:188593 )

• severely impaired hearing

taste/olfaction

impaired olfaction ( J:188593 )

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

growth/size/body

decreased body size ( J:188593 )

• at 2 - 3 weeks of age

decreased body weight ( J:188593 )

• at 2 - 3 weeks of age

• providing damns and pups with alkalinized water rescues the decrease in body weight

behavior/neurological

polydipsia ( J:188593 )

• in mice that receive alkali treatment

abnormal motor coordination/balance ( J:188593 )

• stagger

head tilt ( J:188593 )

circling ( J:188593 )

abnormal sensory capabilities/reflexes/nociception ( J:188593 )

• fail to show a preference for urine from a nonfamiliar animal of the opposite sex over water in an olfactory discrimination assay

absent pinna reflex ( J:188593 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
renal tubular acidosis		DOID:14219	OMIM:179830 OMIM:267200 OMIM:602722	J:188593