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Disturbed water balance in Ku86 −/‐ mice
Author(s) -
Dmitrieva Natalia I,
Chen Henry,
Nussenzweig André,
Burg Maurice B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1159.9
Subject(s) - vasopressin , kidney , medicine , endocrinology , in vivo , biology , urinary system , urine , chemistry , microbiology and biotechnology
High NaCl induces DNA breaks in cells in culture and in the kidney inner medulla in vivo. Ku86 binds to broken ends of damaged DNA and facilitates DNA repair. Ku86 deficiency compromises adaptation of cells to high NaCl, resulting in cellular hypertrophy, cell cycle arrest and chromosomal breakage (PNAS 102:10730,2005). We hypothesized that the renal function of Ku86 −/‐ mice might be impaired because of increased sensitivity of their renal medullary cells to the high NaCl to which they are normally exposed as part of the urinary concentrating mechanism. To analyze the ability of Ku86 −/‐ mice to maintain water balance, mice were subjected to different regimes of water consumption. During free access to water, Ku86 −/‐ mice drink much more water leading to greater urine volume (2.45*±0.26 vs 1.11±0.09 ml/20g of body weight (BW)), and decreased urine osmolality compared to wild type mice. However, their urinary vasopressin excretion (U‐AVP) is significantly higher (271±76* vs 136±22 pg/24h per 20 g of BW). U‐AVP dramatically increases in Ku86 −/‐ mice when water is limited to 3ml per 5g of gel food (599±74* vs 175±30 pg/24h) and they lose weight. Water restriction to 1.7ml/5g causes further weight loss in Ku86 −/‐ mice. We conclude that Ku86 −/‐ mice do not adapt normally to water restriction, possibly due to decreased responsiveness of renal collecting ducts to vasopressin. Supported by the Intramural Programs of NHLBI and NCI.