Diabetes insipidus

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.

Brattleboro rat

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.