Phenotypes Associated with This Genotype

Genotype
MGI:3036453

• Allelic Composition: Slc12a1^tm1Tkh/Slc12a1^tm1Tkh
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

postnatal lethality, complete penetrance ( J:62224 )

• died within 2 weeks of birth

• none survived to weaning unless treated with indomethacin which resulted in about 10% survival past weaning

growth/size/body

postnatal growth retardation ( J:62224 )

• failure to thrive, body weight about 50% that of controls by day 7

hematopoietic system

increased hematocrit ( J:62224 )

• increase can be seen in day 1

• very high at day 7

• remains very high (70%) even after indomethacin treatment

homeostasis/metabolism

abnormal blood homeostasis ( J:62224 )

• blood chemistry is highly abnormal at 7 days

increased circulating creatinine level ( J:62224 )

• plasma levels 3X control levels, discrepancy is even greater if normalized to muscle mass

decreased circulating glucose level ( J:62224 )

• blood glucose levels are very low

increased circulating sodium level ( J:62224 )

• increased sodium concentration

increased circulating total protein level ( J:62224 )

• surviving mice treated with indomethacin develop very high levels of low molecular weight proteins

• particularly males where levels are 4X female levels

• protein is primarily mouse major urinary protein

abnormal fluid regulation ( J:62224 )

• although normal at birth, extracellular fluid volume depletion noticeable in day 1

• after indomethacin treatment turgor returns to normal

increased urine calcium level ( J:62224 )

• urinary calcium excretion is 4X controls while plasma calcium levels are low

increased circulating chloride level ( J:62224 )

metabolic acidosis ( J:62224 )

• metabolic acidosis

increased renin activity ( J:62224 )

• 200X increase in plasma renin levels

• after indomethacin treatment, renin levels return to near normal

renal/urinary system

increased urine calcium level ( J:62224 )

• urinary calcium excretion is 4X controls while plasma calcium levels are low

abnormal kidney morphology ( J:62224 )

hydronephrosis ( J:62224 )

• bilateral hydronephrosis which is not corrected by indomethacin treatment

• dilation of renal collecting system and atrophy of renal parenchyma

abnormal renal tubule morphology ( J:62224 )

• calcification occurs in tubules of survivors treated with indomethacin

nephrocalcinosis ( J:62224 )

• calcification occurs in tubules of survivors treated with indomethacin

abnormal kidney physiology ( J:62224 )

• increased renin expression in the kidney vasculature

• urine is very dilute

kidney failure ( J:62224 )

• severe renal insufficiency

polyuria ( J:62224 )

• very high urine output continues after indomethacin treatment

integument

decreased skin turgor ( J:62224 )

• poor turgor and increased fluid loss by day 7

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bartter disease type 1		DOID:0110142	OMIM:601678	J:62224