Abstract
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.
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Selected References
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- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Durnam D. M., Palmiter R. D. A practical approach for quantitating specific mRNAs by solution hybridization. Anal Biochem. 1983 Jun;131(2):385–393. doi: 10.1016/0003-2697(83)90188-4. [DOI] [PubMed] [Google Scholar]
- Ivell R., Schmale H., Krisch B., Nahke P., Richter D. Expression of a mutant vasopressin gene: differential polyadenylation and read-through of the mRNA 3' end in a frame-shift mutant. EMBO J. 1986 May;5(5):971–977. doi: 10.1002/j.1460-2075.1986.tb04311.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majzoub J. A., Carrazana E. J., Shulman J. S., Baker K. J., Emanuel R. L. Defective regulation of vasopressin gene expression in Brattleboro rats. Am J Physiol. 1987 May;252(5 Pt 1):E637–E642. doi: 10.1152/ajpendo.1987.252.5.E637. [DOI] [PubMed] [Google Scholar]
- Rehbein M., Hillers M., Mohr E., Ivell R., Morley S., Schmale H., Richter D. The neurohypophyseal hormones vasopressin and oxytocin. Precursor structure, synthesis and regulation. Biol Chem Hoppe Seyler. 1986 Aug;367(8):695–704. doi: 10.1515/bchm3.1986.367.2.695. [DOI] [PubMed] [Google Scholar]
- Richter D. Molecular events in expression of vasopressin and oxytocin and their cognate receptors. Am J Physiol. 1988 Aug;255(2 Pt 2):F207–F219. doi: 10.1152/ajprenal.1988.255.2.F207. [DOI] [PubMed] [Google Scholar]
- Schmale H., Heinsohn S., Richter D. Structural organization of the rat gene for the arginine vasopressin-neurophysin precursor. EMBO J. 1983;2(5):763–767. doi: 10.1002/j.1460-2075.1983.tb01497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmale H., Ivell R., Breindl M., Darmer D., Richter D. The mutant vasopressin gene from diabetes insipidus (Brattleboro) rats is transcribed but the message is not efficiently translated. EMBO J. 1984 Dec 20;3(13):3289–3293. doi: 10.1002/j.1460-2075.1984.tb02291.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmale H., Richter D. Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats. Nature. 1984 Apr 19;308(5961):705–709. doi: 10.1038/308705a0. [DOI] [PubMed] [Google Scholar]
- VALTIN H., SCHROEDER H. A. FAMILIAL HYPOTHALAMIC DIABETES INSIPIDUS IN RATS (BRATTLEBORO STRAIN). Am J Physiol. 1964 Feb;206:425–430. doi: 10.1152/ajplegacy.1964.206.2.425. [DOI] [PubMed] [Google Scholar]