Familial Neurohypophysial Diabetes Insipidus in a Large Dutch Kindred: Effect of the Onset of Diabetes on Growth in Children and Cell Biological Defects of the Mutant Vasopressin Prohormone1
| Autor: | R. Zalm, J. Peter H. Burbach, Henk Engel, Erica L T van den Akker, Marga Nijenhuis, Andre P. Abbes, A.A.M. Franken, David de Wied |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Arginine vasopressin receptor 1B
medicine.medical_specialty Vasopressin Endocrinology Diabetes and Metabolism Biochemistry (medical) Clinical Biochemistry Prohormone Mutant Autosomal dominant trait Neuropeptide Biology medicine.disease Biochemistry Endocrinology Arginine vasopressin receptor 2 Internal medicine Diabetes insipidus medicine hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 86:3410-3420 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.86.7.7686 |
| Popis: | Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant trait in which expression of a mutant vasopressin prohormone reduces vasopressin production. We investigated the NP85 Cys→Gly mutant vasopressin prohormone in a large kindred in The Netherlands. We demonstrate that growth retardation is an important early sign in two children from this kindred, which recuperates by substitution therapy with 1-desamino-8-d-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of FNDI, we analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. This defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic r... |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|