mortality/aging
• significantly fewer homozygotes are obtained from heterozygous intercrosses, suggesting reduced prenatal lethality
|
renal/urinary system
• after water deprivation for 36 hrs, 80% of homozygotes display a urine sodium concentration of less than 10 mM
|
• euhydrated homozygotes exhibit a markedly low urine osmolality (580-610 mOsm) that does not increase after water deprivation for 36 hrs; in contrast, average urine osmolality in control mice is 1400 mOsm before water deprivation and increases to ~3000 mOsm after deprivation
• i.p. injection of the V2 receptor agonist DDAVP fails to cause a further increase in urine osmolality, indicating that the urinary concentrating defect does not involve central osmoreceptor sensing
|
• homozygotes show an ~8-fold reduction of osmotic water permeability (Pf) in apical membrane vesicles from kidney proximal tubules relative to wild-type mice
(J:45888)
• the low urine Na+ concentration after water deprivation and absence of DDAVP effect, which should equalize urine and medullary interstitial osmolalities, indicate that homozygotes are unable to generate a hypertonic medullary interstitium by countercurrent multiplication
(J:45888)
• water permeability of the brush-border membrane vesicles from the outer medulla is lower than that of wild-type
(J:102454)
|
homeostasis/metabolism
• after water deprivation for 36 hrs, homozygotes exhibit significant serum hyperosmolality relative to similarly-treated control mice (517 mOsm vs 311-325 mOsm, respectively)
• however, nearly all homozygotes can be resuscitated by oral water administration without morbidity
|
dehydration
(
J:45888
)
• after water deprivation for 36 hrs, homozygotes appear severely dehydrated whereas wild-type mice appear grossly normal
|
• after water deprivation for 36 hrs, 80% of homozygotes display a urine sodium concentration of less than 10 mM
|
• euhydrated homozygotes exhibit a markedly low urine osmolality (580-610 mOsm) that does not increase after water deprivation for 36 hrs; in contrast, average urine osmolality in control mice is 1400 mOsm before water deprivation and increases to ~3000 mOsm after deprivation
• i.p. injection of the V2 receptor agonist DDAVP fails to cause a further increase in urine osmolality, indicating that the urinary concentrating defect does not involve central osmoreceptor sensing
|
behavior/neurological
• after water deprivation for 36 hrs, homozygotes become markedly lethargic and in some cases unresponsive, whereas wild-type mice remain active
|
growth/size/body
• after water deprivation for 36 hrs, homozygotes exhibit a significantly greater reduction in average body weight relative to similarly-treated wild-type mice (35% vs 20-22%, respectively)
|
• homozygotes are physically normal but exhibit a mild growth retardation relative to wild-type mice
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endocrine/exocrine glands
N |
• homozygotes display no defects in the volume or composition of saliva, as revealed by pilocarpine stimulation studies
|