Analysis Tools
renal/urinary system
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• male hemizygotes exhibit hyperactivation of the SPAK/OSR1 and Na+Cl- cotransporter (NCC) pathway in the distal convoluted tubules of the kidney
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cardiovascular system
hypertension
(
J:221240
)
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• male hemizygotes exhibit a late-onset mild hypertension
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• at 7, 14 and 21 days after dietary NaCl loading, male hemizygotes show a significantly increased SBP at the age of 13 weeks (i.e. earlier than the spontaneous hypertension), unlike similarly treated wild-type controls where SBP is slightly decreased, as determined by the tail-cuff method
• at day 15 after the start of NaCl loading, male hemizygotes show a significantly higher SBP than wild-type controls in the first half of the dark period, as measured by telemetry
• in contrast, the diastolic blood pressure is modestly, but not significantly elevated at 15 days after the start of NaCl loading
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• male hemizygotes show a significantly increased systolic blood pressure (SBP) along with aging, reaching 115.9 +/- 3.6mmHg at 30 weeks, whereas that of age-matched wild-type controls is only slightly increased (109.3 +/- 1.5mmHg)
• no significant differences in SBP are detected at 14 weeks of age
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cellular
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• mutant MEFs exposed to hypotonic stress exhibit accelerated activation of oxidative stress-responsive kinase 1 (OSR1)
• hyperactivation of OSR1 in mutant MEFs is suppressed (rescued) by exogenous MAP3K15 expressed via adenovirus infection
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homeostasis/metabolism
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N |
• male hemizygotes display no significant changes in plasma or urine electrolytes (including K+ concentrations) relative to wild-type controls
• no alterations in plasma creatinine and BUN levels or urine creatinine levels are observed
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