Immunocytochemical evidence for the presence of vasopressin in intermediate sized neurosecretory granules of solitary neurohypophyseal terminals in the homozygous brattleboro rat

• Published in: Neuroscience Vol. 72; no. 1; pp. 225 - 231
• Main Authors: Sonnemans, M.A.F., Evans, D.A.P., Burbach, J.P.H., van Leeuwen, F.W.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-05-1996; Elsevier
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cytoplasmic Granules - metabolism; diabetes insipidus; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; hypothalamus; Immunohistochemistry; Male; Medical sciences; Microscopy, Electron; Microscopy, Immunoelectron; Molecular Sequence Data; Mutation; neurophysin; Neurosecretory Systems - metabolism; Neurosecretory Systems - ultrastructure; paraventricular nucleus; Pituitary Gland, Posterior - metabolism; Pituitary Gland, Posterior - ultrastructure; Presynaptic Terminals - metabolism; Presynaptic Terminals - ultrastructure; Rats; Rats, Brattleboro; Solitary Nucleus - metabolism; Solitary Nucleus - ultrastructure; supraoptic nucleus; Vasopressins - metabolism; SON; DAB; diabetes insipidus; di; supraoptic nucleus; PVN; neurophysin; ER; hypothalamus; di/di; NL; paraventricular nucleus; Endocrinopathy; Animal model; Rat; Immunocytochemistry; Diabetes insipidus; Peptide hormone; Rodentia; Central nervous system; Neurosecretory granule; Hypothalamus; Paraventricular nucleus; Gene expression; Electron microscopy; Neuropeptide; Vasopressin; Vertebrata; Mammalia; Animal; Hormonal investigation; Supraoptic nucleus; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(95)00550-1

A single base deletion (ΔG) in the vasopressin gene is the cause of diabetes insipidus in the homozygous Brattleboro rat (di/di). The resulting frameshift leads to the expression of an aberrant vasopressin precursor which is unable to enter the secretory pathway, thereby preventing vasopressin biosynthesis. In a small number of solitary magnocellular hypothalamic neurons within the supraoptic and paraventricular nuclei, the reading frame is restored by a dinucleotide (ΔGA) frameshift mutation, at two separate GAGAG motifs downstream of the original G-deletion. This results in two + 1 di-vasopressin precursors that are still partially mutated within the neurophysin region.
The present study provides immunocytochemical evidence which demonstrates that, within magnocellular solitary neurons of the supraoptic and paraventricular nuclei of the di/di rat, the + 1 di-vasopressin precursors can enter the secretory pathway followed by their enzymatic processing into vasopressin during axonal transport to the neural lobe. However, the cellular characteristics of biosynthesis are different from those of wild-type rats. Immunoelectron microscopical localization of vasopressin gene products in the neural lobe of di/di rats revealed their presence in neurosecretory granules, the diameter of which is intermediate (116 nm) between those of the neurosecretory granules in the di/di (80–100 nm) and wild-type (160 nm) rats.