Phenotypes Associated with This Genotype

Genotype
MGI:3041878

• Allelic Composition: Kcnj1^tm1Ges/Kcnj1^tm1Ges
• Genetic Background: involves: 129X1/SvJ * Black Swiss

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

Kcnj1^tm1Ges/Kcnj1^tm1Ges mice exhibit hydronephrosis

mortality/aging

postnatal lethality, incomplete penetrance ( J:79354 )

• approximately 95% of homozygotes died before 3 weeks of age; 85% of mutants died by 12 days of age, and only 5% survived to weaning

• mutans that survived to weaning almost invariably survived to adulthood, appeared slightly smaller but were healthy

• daily subcutaneous injections of either indomethacin or isotonic saline failed to prolong survival

behavior/neurological

polydipsia ( J:79354 )

cardiovascular system

decreased systemic arterial blood pressure ( J:79354 )

growth/size/body

postnatal growth retardation ( J:79354 )

• homozygotes displayed a significant reduction in body weight and failed to thrive

hematopoietic system

increased hematocrit ( J:79354 )

homeostasis/metabolism

increased circulating sodium level ( J:79354 )

• adult mutants exhibited elevated blood concentrations of Na+ and Cl-

dehydration ( J:79354 )

metabolic acidosis ( J:79354 )

• homozygous null adult mice displayed metabolic acidosis, volume depletion, and dehydration

abnormal urine homeostasis ( J:79354 )

• the urine electrolyte excretion rate in null mutants was not significantly different from that of wild-type mice (except that chloride excretion was mildly increased), but because of the low glomerular filtration rate in the mutant animals, fractional excretions of Na+, K+, Cl-, and solutes were significantly increased relative to wild-type

decreased urine osmolality ( J:79354 )

• adult homozygotes displayed poor urinary concentrating ability

renal/urinary system

abnormal urine homeostasis ( J:79354 )

• the urine electrolyte excretion rate in null mutants was not significantly different from that of wild-type mice (except that chloride excretion was mildly increased), but because of the low glomerular filtration rate in the mutant animals, fractional excretions of Na+, K+, Cl-, and solutes were significantly increased relative to wild-type

decreased urine osmolality ( J:79354 )

• adult homozygotes displayed poor urinary concentrating ability

hydronephrosis ( J:79354 )

• homozygotes exhibited hydronephrosis prior to weaning

decreased renal glomerular filtration rate ( J:79354 )

• the whole kidney glomerular filtration rate was reduced in null mice, to approximately 10-15% of that in wild-type mice

• the single nephron glomerular filtration rate (SNGFR) was relatively unaffected and NaCl absorption in the thick ascending limb was reduced but not eliminated

decreased tubuloglomerular feedback response ( J:79354 )

• tubuloglomerular feedback was severely impaired

polyuria ( J:79354 )

• adult homozygotes displayed polyuria

integument

wrinkled skin ( J:79354 )

decreased skin turgor ( J:79354 )

• homozygotes displayed poor turgor and wrinkled skin, probably due to fluid volume depletion

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bartter disease type 2		DOID:0110143	OMIM:241200	J:79354