Phenotypes Associated with This Genotype

Genotype
MGI:5526103

• Allelic Composition: Scnn1a^tm1Rss/Scnn1a^tm1Rss; Tg(CMV-Scnn1a)1352Rss/0
• Genetic Background: involves: 129P2/OlaHsd * NMRI

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:43583 )

• 44% of mutants die within the first 2 weeks of life

• overall survival rate of females is lower (11%) compared with males (64%)

digestive/alimentary system

decreased intestinal epithelial sodium ion transmembrane transport ( J:43583 )

• adults exhibit lower amiloride-sensitive rectal potential difference compared to wild-type mice

• sodium transport across the rectal epithelium is decreased

growth/size/body

postnatal growth retardation ( J:43583 )

• mutants are smaller shortly after birth and even though rate of growth is similar to controls after the 2nd week of life, mutants continue to be smaller into adulthood

homeostasis/metabolism

increased circulating aldosterone level ( J:43583 )

• adult survivors show a compensated pesudohypoaldosteronism with normal acid/base and electrolyte values but a 6-fold elevation of plasma aldosterone

• however, serum corticosternone levels are normal

decreased urine bicarbonate level ( J:43583 )

• 12 hours after birth, mutants show normal bicarbonate levels, however, in 5 to 9 day old mutants, bicarbonate levels are decreased and then normalize in adults

abnormal renal sodium reabsorption ( J:43583 )

• 5 to 9 day old mutants exhibit impaired renal sodium absorption, however improvement in absorption is seen in adults

increased urine sodium level ( J:43583 )

• by 5-9 days after birth, mutants show significant urinary salt-wasting [Na+] with no significant decrease in urinary potassium levels indicating abnormal renal sodium absorption

• however adults show normal sodium levels

• the urinary sodium to potassium ratio is higher in 5 to 9 day old mutants but is normal in adults

metabolic acidosis ( J:43583 )

• by 5-9 days of age, mutants show metabolic acidosis

decreased urine pH ( J:43583 )

• 12 hours after birth, mutants show normal pH, however, pH is decreased in 5 to 9 day old mutants but then becomes normal in adults

renal/urinary system

decreased urine bicarbonate level ( J:43583 )

• 12 hours after birth, mutants show normal bicarbonate levels, however, in 5 to 9 day old mutants, bicarbonate levels are decreased and then normalize in adults

abnormal renal sodium reabsorption ( J:43583 )

• 5 to 9 day old mutants exhibit impaired renal sodium absorption, however improvement in absorption is seen in adults

increased urine sodium level ( J:43583 )

• by 5-9 days after birth, mutants show significant urinary salt-wasting [Na+] with no significant decrease in urinary potassium levels indicating abnormal renal sodium absorption

• however adults show normal sodium levels

• the urinary sodium to potassium ratio is higher in 5 to 9 day old mutants but is normal in adults

decreased urine pH ( J:43583 )

• 12 hours after birth, mutants show normal pH, however, pH is decreased in 5 to 9 day old mutants but then becomes normal in adults

respiratory system

respiratory system phenotype ( J:43583 )

N • mutants are able to clear fetal liquid from the air spaces at 12 hours of age and surviving adults have normal or near normal liquid absorption in the lungs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive pseudohypoaldosteronism type 1		DOID:0060854	OMIM:264350	J:43583