Phenotypes Associated with This Genotype

Genotype
MGI:3639115

• Allelic Composition: Aqp2^cph/Aqp2^cph
• Genetic Background: C57BL/6J-Aqp2^cph

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

Small size and congenital obstruction in Aqp2^cph/Aqp2^cph mice

mortality/aging

premature death ( J:9451 , J:13746 , J:109463 )

• most die by 1 to 2 months of age but a few survive to adulthood and can breed (J:9451)

• few live beyond 2 months of age (J:13746)

• 90% die between 2 to 4 weeks of age while the remaining 10% survive past weaning with the oldest reaching 10 months of age (J:109463)

renal/urinary system

abnormal urine homeostasis ( J:109463 )

• fail to concentrate urine in response to [deamino-Cys¹, D-Arg⁸]-vasopressin treatment; however, there is no significant difference in the excretion of Na and K as indicated by urinary sodium creatinine and potassium/creatinine ratios

colorless urine ( J:9451 )

• by 2 weeks of age urine is colorless

abnormal kidney morphology ( J:9451 , J:109463 )

• at P10, focal loss of the parenchyma is seen (J:9451)

• pathological changes related to obstructive nephropathy (J:109463)

dilated kidney collecting duct ( J:109463 )

kidney collecting duct atrophy ( J:109463 )

• parenchymal atrophy

abnormal kidney pyramid morphology ( J:9451 )

• at P10, partial erosion of the pyramids is seen

kidney medulla atrophy ( J:9451 )

• by P20 medullary tissue is generally absent except at the base of the papillae and a thin rim of focal remnants surrounding the enlarged caliceal space

abnormal kidney pelvis morphology ( J:109463 )

• expansion of the pelvicocaliceal space

• erosion probably the result of obstructive nephropathy

kidney papillary atrophy ( J:9451 )

• at P1, slight erosion of the renal papillae is seen with the average diameter reduced to 0.32 mm compared to 0.45 mm in control mice

• as mice age a progressive narrowing of the papillar diameter is seen

dilated kidney calyx ( J:9451 )

• starting at P1, progressive widening of the calyceal space and narrowing of the papillar diameter is seen

hydronephrosis ( J:9451 , J:109463 )

• by 20 days of age in most mice both kidneys are massively enlarged and appear as tense, fluid-filled shells with cortical and medullary wasting (J:9451)

• mice under 14 days of age show unilateral or bilateral hydronephrosis while almost all mice older than 14 days show severe bilateral hydronephrosis (J:109463)

• about 66% of mice have more severe defects in the right kidney, about 23% have more defects in the left kidney and 11% have both kidneys equally affected (J:109463)

• however, in most cases there does not appear to be a physical blockage of urine transport (J:109463)

hydroureter ( J:109463 )

• hydroureter and an apparent obstruction of the ureterovesical junction are seen in only about 25% of mice

ureterovesical junction obstruction ( J:9451 )

• hydroureter and an apparent obstruction of the ureterovesical junction are seen in only about 25% of mice

polyuria ( J:109463 )

homeostasis/metabolism

increased blood osmolality ( J:109463 )

• elevated serum osmolality

increased blood urea nitrogen level ( J:9451 , J:109463 )

• at P20 (J:9451)

abnormal urine homeostasis ( J:109463 )

• fail to concentrate urine in response to [deamino-Cys¹, D-Arg⁸]-vasopressin treatment; however, there is no significant difference in the excretion of Na and K as indicated by urinary sodium creatinine and potassium/creatinine ratios

colorless urine ( J:9451 )

• by 2 weeks of age urine is colorless

behavior/neurological

lethargy ( J:9451 , J:109463 )

• by 2 weeks of age (J:9451)

growth/size/body

decreased body size ( J:9451 , J:13746 , J:109463 )

• visible almost from birth (J:13746)

• by P8 (J:109463)

decreased body weight ( J:9451 , J:109463 )

• at 15 days of age average weight is 4.10 g compared to 7.25 g for control littermates (J:9451)

• at 20 days of age average weight is 4.98 g compared to 12.51 g for control littermates (J:9451)

• by P8 (J:109463)

postnatal growth retardation ( J:109463 )

distended abdomen ( J:9451 , J:13746 , J:109463 )

• enlarged abdomen at 2 weeks of age (J:13746)

reproductive system

infertility ( J:109463 )

• adults are either infertile or show mildly reduced fertility

reduced fertility ( J:109463 )

• adults are either infertile or show mildly reduced fertility

integument

alopecia ( J:9451 )

• by 2 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrogenic diabetes insipidus		DOID:12387		J:109463