Diabetes insipidus is a "disease that is characterized by frequent urination, excretion of large amounts of dilute urine, and excessive thirst. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or vasopressin) secreted by the neurohypophysis (posterior pituitary gland), impaired kidney response to ADH, and impaired hypothalamic regulation of thirst."
There are two basic forms of diabetes insipidus. Hypothalamic diabetes insipidus is the inability to produce or secrete vasopressin, and can be treated with vasopressin agonists. Nephrogenic diabetes insipidus is the inability to respond to vaopressin, (for instance if there is a mutation affecting the V2 vasopressin receptor) and cannot be treated in this way.
In humans, familial hypothalamic diabetes insipidus is most commonly a consequence of a point mutation in the vasopressin gene, usually in the region coding for vasopressin-associated neurophysin. Such mutations impair the folding of the precursor peptide, and aberrant protein accumulates in the neurons, ultimately causing them to fail.
The Brattleboro rat strain has hereditary hypothalamic diabetes insipidus. The mutation is in the coding region of the vasopressin gene; a single base deletion in the second exon gives rise to an open reading frame. The defect affects not the vasopressin coding region but the region coding the associated neurophysin; as a result of the deletion, the homozygous (di/di) Brattleboro rat produces a mutant precursor with a different carboxyl terminus and no stop codon. The precursor includes the vasopressin sequence; however the aberrent form of the precursor protein means that it cannot be properly processed and packaged into neurosecretory vesicles. Accordingly there is no detectable vasopressin secreted into the blood.
The homozygous Brattleboro rat drinks about its own body weight of water each day and excretes copious amounts of very dilute urine. These defects can be treated very effectively by giving the rats vasopressin. The Brattleboro rat strain (named after West Brattleboro, Vermont; the location of the animal house where the founders of the strain were first identified in 1961) became very important in achieving a basic understanding of the physiological principles underlying the actions and roles of vasopressin.
- Anonymous (2023), Diabetes insipidus (English). Medical Subject Headings. U.S. National Library of Medicine.
- Arima H, Oiso Y (2010) Mechanisms underlying progressive polyuria in familial neurohypophysial diabetes insipidus J Neuroendocrinol 22:754-7 PMID 20492364
- Christensen JH, Rittig S (2006) Familial neurohypophyseal diabetes insipidus--an update Semin Nephrol 26:209-23 PMID 16713494
- Sawyer WH et al. (1964) Neurohypophysial principles in rats with familial hypothalamic diabetes insipidus (Brattleboro strain) Endocrinology 74:153-5 PMID 14114664
- Kim JK, Schrier RW (1998) Vasopressin processing defects in the Brattleboro rat: implications for hereditary central diabetes insipidus in humans? Proc Assoc Am Physicians 110:380-6 PMID 9756087
- Morris JF (1982) The Brattleboro magnocellular neurosecretory system: a model for the study of peptidergic neurons Ann N Y Acad Sci 394:54-71 PMID 6758654
- Pickering BT, North WG (1982) Biochemical and functional aspects of magnocellular neurons and hypothalamic diabetes insipidus Ann N Y Acad Sci 394:72-81 PMID 6185029
- Sokol HW, Zimmerman EA (1982) The hormonal status of the Brattleboro rat Ann N Y Acad Sci 394:535-48 PMID 6295231