Arginine vasopressin gene regulation in the homozygous Brattleboro rat.
The Brattleboro rat, which has an autosomally recessive form of diabetes insipidus, has been reported to have a marked defect in the regulation of arginine vasopressin (AVP) gene expression. However, it is not known whether this is a primary genetic defect or occurs secondary to the urinary water losses which occur in the absence of circulating AVP in the Brattleboro rat. This present study was therefore undertaken to study AVP gene regulation in the Brattleboro rat after chronic AVP treatment by osmotic minipump for 2 wk. In Brattleboro rats without AVP treatment, neither urinary osmolality (Uosm) nor hypothalamic AVP mRNA was significantly changed after 24 h of fluid deprivation (Uosm, 413 +/- 33 to 588 +/- 44, NS; AVP mRNA, 39.33 +/- 2.95 to 46.39 +/- 2.71 pg/micrograms total RNA, NS). In contrast, when Brattleboro rats were treated with AVP for 2 wk, the regulation of AVP gene occurred in response to 24 h of fluid deprivation. In these studies, hypothalamic AVP mRNA was significantly increased compared with the Brattleboro rats still receiving AVP with free access of water (28.9 +/- 3.5 vs. 65.0 +/- 3.3 pg/micrograms total RNA, P less than 0.001). Further studies in Long-Evans rats demonstrate a similar response to a comparable degree of fluid deprivation as Uosm and AVP mRNA were significantly increased after 72 h of fluid deprivation (Uosm, 1,505 +/- 186 to 5,460 +/- 560 mosmol/kg, P less than 0.001; AVP mRNA, 31.7 +/- 3.9 to 77.5 +/- 4.6 pg/micrograms total RNA, P less than 0.001). These results indicate that AVP-replaced homozygous Brattleboro rats can regulate AVP gene expression normally in response to fluid deprivation. This finding indicates that the defect in AVP gene regulation in the Brattleboro rat not receiving AVP replacement is a secondary phenomenon rather than a primary genetic defect.
Kim
J K
JK
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Soubrier
F
F
Michel
J B
JB
Bankir
L
L
Corvol
P
P
Schrier
R W
RW
D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics* / Q000494:pharmacology; D003919:Diabetes Insipidus / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D015870:Gene Expression; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011910:Rats, Brattleboro / Q000235:genetics* / Q000502:physiology; D011922:Rats, Mutant Strains / Q000235:genetics*; D014882:Water-Electrolyte Balance
D012333:RNA, Messenger; D001127:Arginine Vasopressin