Hereditary and Idiopathic Types of Diabetes Insipidus

Green, John R.; Buchan, G. C.; Alvord, Ellsworth C.; Swanson, August G.

doi:10.1093/brain/90.3.707

Cited by 99 publications

(41 citation statements)

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“…Symptoms of diabetes insipidus, such as polyuria, polydipsia, and thirst, usually manifest several months or years after birth. A limited number of autopsy studies have reported a paucity of AVP-producing neurons in the hypothalamus of patients with FNDI (2)(3)(4)(5), leading to the hypothesis that progressive degeneration of AVP-producing cells might be involved in the pathogenesis of the disease.…”

Section: Familial Neurohypophyseal Diabetes Insipidus (Fndi)mentioning

confidence: 99%

A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons

Russell

Ito²,

Ito³

et al. 2003

J. Clin. Invest.

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Section: Familial Neurohypophyseal Diabetes Insipidus (Fndi)mentioning

confidence: 99%

A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons

Russell

Ito²,

Ito³

et al. 2003

J. Clin. Invest.

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“…Vasopressin and neurophysin II associate after cleavage and then form the tetramer, which increases the binding affinity of vasopressin for neurophysin II. Autopsy studies of patients with a familial form of diabetes insipidus showed a markedly subnormal number of magnocellular neurons and associated moderate gliosis [40, 41], suggesting the disorder was due to a dysgenesis or degeneration of these hypothalamic neurons.…”

Section: Etiology Of Diabetes Insipidusmentioning

confidence: 99%

Diabetes insipidus

Maghnie¹

2003

Horm Res Paediatr

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Diabetes insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. In many patients, it is caused by the destruction or degeneration of the neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. Known causes of these lesions include: germinoma or craniopharyngioma; Langerhans cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma following surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Magnetic resonance imaging (MRI) allows identification of the posterior pituitary hyperintensity and of hypothalamic-pituitary abnormalities. Thickening of the pituitary stalk is the second most common finding on MRI scans in several local inflammatory pathologies and autoimmune diseases or germinoma, but it is not specific to any single subtype. A progressive increase in the size of the anterior pituitary gland should alert physicians to the possibility that a germinoma is present, whereas a decrease can suggest the presence of an inflammatory or autoimmune process. Most children with acquired central diabetes insipidus and a thickened pituitary stalk have anterior pituitary hormone deficiencies during follow-up. Biopsy of enlarged pituitary stalk should be reserved for patients with a hypothalamic-pituitary mass and progressive thickening of the pituitary stalk, since spontaneous recovery may occur.

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“…Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) shows a high penetrance, with symptoms beginning weeks to months after birth. Postmortem histological studies of affected individuals have shown degeneration of the vasopressinergic magnocellular neurons (Bergeron et al, 1991;Braverman et al, 1965;Green et al, 1967;Nagai et al, 1984). A knock-in mouse model expressing the human pathogenic mutant C67X (Cys67 of NPII mutated to a stop codon) confirmed the neurotoxic effect of the mutant protein on vasopressinergic cells (Russell et al, 2003), but the mechanism causing cell death remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Dominant pro-vasopressin mutants that cause diabetes insipidus form disulfide-linked fibrillar aggregates in the endoplasmic reticulum

Birk

Friberg

Prescianotto-Baschong

et al. 2009

Journal of Cell Science

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To assay for secretion, wild-type pro-vasopressin, the recessive mutant P7L, and the dominant mutants ⌬E47, Y2H, C28Y and ⌬G227 were expressed in COS-1 cells, pulse-labeled with [ 35 S]methionine/cysteine, chased for 2 hours, isolated from the cells and from the media by immunoprecipitation, and analyzed by SDSgel electrophoresis and autoradiography ( Fig. 2A). As expected, a considerable fraction of the wild type and of P7L was recovered from the media, reflecting their ability to fold and pass ER quality control. By contrast, the dominant mutants ⌬E47, Y2H and C28YAutosomal dominant neurohypophyseal diabetes insipidus results from mutations in the precursor protein of the antidiuretic hormone arginine vasopressin. Mutant prohormone is retained in the endoplasmic reticulum of vasopressinergic neurons and causes their progressive degeneration by an unknown mechanism. Here, we show that several dominant provasopressin mutants form disulfide-linked homo-oligomers and develop large aggregations visible by immunofluorescence and immunogold electron microscopy, both in a fibroblast and a neuronal cell line. Double-labeling showed the pro-vasopressin aggregates to colocalize with the chaperone calreticulin, indicating that they originated from the endoplasmic reticulum.The aggregates revealed a remarkable fibrillar substructure. Bacterially expressed and purified mutant pro-vasopressin spontaneously formed fibrils under oxidizing conditions. Mutagenesis experiments showed that the presence of cysteines, but no specific single cysteine, is essential for disulfide oligomerization and aggregation in vivo. Our findings assign autosomal dominant diabetes insipidus to the group of neurodegenerative diseases associated with the formation of fibrillar protein aggregates.

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Hereditary and Idiopathic Types of Diabetes Insipidus

Cited by 99 publications

References 0 publications

A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons

A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons

Diabetes insipidus

Dominant pro-vasopressin mutants that cause diabetes insipidus form disulfide-linked fibrillar aggregates in the endoplasmic reticulum

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