Phenotypes Associated with This Genotype

Genotype
MGI:3664199

• Allelic Composition: Scnn1g^tm1Bhk/Scnn1g^tm1Bhk
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

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

digestive/alimentary system

decreased intestinal epithelial sodium ion transmembrane transport ( J:50528 )

• all distal colonic explants from postnatal mutants show low basal short circuit currents (ISC) and no response to amiloride compared to wild-type and heterozygous preparations which show significant amiloride-mediated inhibition

mortality/aging

postnatal lethality, incomplete penetrance ( J:50528 )

• 6 of 20 pups died spontaneously between 24 and 36 hours of life

behavior/neurological

lethargy ( J:50528 )

• from 12 hours after birth onward, homozygotes become progressively less active; at 24 hours, homozygotes are lethargic and pale

homeostasis/metabolism

increased circulating potassium level ( J:50528 )

• homozygous pups show an increase in serum K+ from 4 hours after birth to 24 hours (15.8 mEq/l at 4 hours to 18.3 mEq/l at 24 hours; wild-type and heterozygous pups show a decline from 12.6 to 9.7 mEq/l during this period

decreased circulating sodium level ( J:50528 )

• homozygotes show lower serum sodium levels at 24 hours compared to wild-type and heterozygotes

increased urine bicarbonate level ( J:50528 )

• bicarbonate levels in urine of homozygotes tends to be higher but differences do not reach statistical significance

decreased urine potassium level ( J:50528 )

• K+ concentration in urine from homozygotes is lower than that of wild-type or heterozygotes independent of urine volume at 4, 12 and 24 hours

increased urine sodium level ( J:50528 )

• Na+ concentration in urine is higher in homozygotes than wild-type or heterozygotes independent of urine volume at 4, 12 and 24 hours

renal/urinary system

increased urine bicarbonate level ( J:50528 )

• bicarbonate levels in urine of homozygotes tends to be higher but differences do not reach statistical significance

decreased urine potassium level ( J:50528 )

• K+ concentration in urine from homozygotes is lower than that of wild-type or heterozygotes independent of urine volume at 4, 12 and 24 hours

increased urine sodium level ( J:50528 )

• Na+ concentration in urine is higher in homozygotes than wild-type or heterozygotes independent of urine volume at 4, 12 and 24 hours

oliguria ( J:50528 )

• volume collected from homozygotes is lower than wild-type or heterozygous littermates at 12 and 24 hours after birth; in controls, output increases from 3.9 ul at 4 hours to 11.9 ul at 24 hours while homozygous pup output remains low (5.9 ul - 4 hours, 4.2 ul at 24 hours)

respiratory system

increased wet-to-dry lung weight ratio ( J:50528 )

• wet/dry lung weights are similar between all genotypes at birth; wet/dry weight in wild-type and heterozygotes decreases at 4 hours to values comparable to 12 and 24 hour values and adult lung values while homozygotes show little change between 4 and 24 hours indicating very little water clearance from their lungs especially at 4 hours compared to littermates

decreased respiratory epithelial sodium ion transmembrane transport ( J:50528 )

• transepithelial bioelectric properties are altered in mutant epithelia; mean change of basal potential difference (PD) in tracheal epithelial explants (-5%) after amiloride treatment is less than that of wild-type explants (-24%) inhibition by amiloride

• 5/17 tracheal explants show 8-15% inhibition by amiloride

growth/size/body

weight loss ( J:50528 )

• pups consistently lose weight from 12 hours after birth

integument

pallor ( J:50528 )

• at 24 hours, pups are lethargic and pale compared to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive pseudohypoaldosteronism type 1		DOID:0060854	OMIM:264350	J:50528