Phenotypes Associated with This Genotype

Genotype
MGI:3575012

• Allelic Composition: Umod^tm1Kuma/Umod^tm1Kuma
• Genetic Background: involves: 129

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

homeostasis/metabolism

abnormal urine homeostasis ( J:245853 )

• urinary TNF-alpha levels are greater under baseline conditions

increased urine chloride ion level ( J:245853 )

• mutants exhibit greater urine chloride excretion than wild-type mice during salt loading

increased urine potassium level ( J:245853 )

• mutants exhibit greater urine potassium excretion than wild-type mice during salt loading

increased urine sodium level ( J:245853 )

• average 24-hour urinary sodium excretion is greater than in wild-type mice after salt loading with 2% NaCl

abnormal urine osmolality ( J:96653 )

• osmolar excretion in water deprived mice is not reduced to the same level as in wildtype, indicating inability to concentrate urine

cardiovascular system

decreased systemic arterial systolic blood pressure ( J:245853 )

• systolic blood pressure is lower under basal conditions

decreased susceptibility to hypertension ( J:245853 )

• administration of 2% NaCl does not alter systolic blood pressure in mutants whereas it increases it in wild-type mice

• however, no differences are seen between 2% salt-loaded wild-type and mutant mice for diastolic pressure, mean arterial pressure, heart rate, or motor activity

renal/urinary system

abnormal urine homeostasis ( J:245853 )

• urinary TNF-alpha levels are greater under baseline conditions

increased urine chloride ion level ( J:245853 )

• mutants exhibit greater urine chloride excretion than wild-type mice during salt loading

increased urine potassium level ( J:245853 )

• mutants exhibit greater urine potassium excretion than wild-type mice during salt loading

increased urine sodium level ( J:245853 )

• average 24-hour urinary sodium excretion is greater than in wild-type mice after salt loading with 2% NaCl

abnormal urine osmolality ( J:96653 )

• osmolar excretion in water deprived mice is not reduced to the same level as in wildtype, indicating inability to concentrate urine

abnormal kidney morphology ( J:245853 )

• kidney shows diffuse edema with cellular and interstitial swelling in the papillary tissue both before and after salt loading

abnormal juxtaglomerular apparatus morphology ( J:96653 )

• gene expression of paracrine/endocrine components of the juxtaglomerular apparatus is decreased

abnormal loop of Henle ascending limb thick segment morphology ( J:96653 )

• significant upregulation of major ion transporters/channels along the thick ascending limb cells of Henle's loop

decreased creatinine clearance ( J:96653 , J:245853 )

• creatinine clearance is 63% lower than in wild-type mice (J:96653)

• mice exhibit decreased creatinine clearance at baseline (J:245853)

increased creatinine clearance ( J:245853 )

• creatinine clearance is increased during salt loading with 2% NaCl

decreased renal glomerular filtration rate ( J:96653 , J:245853 )

• the glomerular filtration rate as estimated by creatinine clearance is reduced, however the kidneys are normal and no differences in serum electrolyte, liver function, lipid values, water consumption, osmolar excretion, or sodium, potassium, and uric acid excretion are seen (J:96653)

• mice exhibit decreased glomerular filtration rate at baseline as indicated by decreased creatinine clearance (J:245853)

increased renal glomerular filtration rate ( J:245853 )

• mice show increased glomerular filtration rate compared to wild-type mice during salt loading

polyuria ( J:96653 , J:245853 )

• mice are unable to concentrate their urine to the same degree as controls when deprived of water and excrete higher urine volumes than wildtype without significantly elevated electrolyte losses (J:96653)

• mutants exhibit greater urine volume than wild-type mice during salt loading (J:245853)

growth/size/body

weight loss ( J:245853 )

• mice exhibit a lower body weight at weeks 1, 2, 4, 5, and 6 of salt loading unlike wild-type mice which show unchanged body weight

behavior/neurological

increased fluid intake ( J:245853 )

• mice show a greater fluid intake during 6 weeks of salt loading than wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial juvenile hyperuricemic nephropathy		DOID:0060062	OMIM:162000 OMIM:613092 OMIM:614227	J:96653