Propressophysin is present in neurones at multiple sites in wistar and homozygous brattleboro rat brain

Leeuwen, Fred W. van; Caffé, Romeo; Sluis, P.J. van der; Sluiter, A.A.; Woude, T.P. van der; Seidah, Nabil G.; Chrétien, Michel

doi:10.1016/0006-8993(86)90272-6

Cited by 21 publications

(9 citation statements)

References 30 publications

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“…These predicted precursors explain the wild-type phenotype of the reverted magnocellular neurons of di/di rats as detected previously by immunocytochemistry (2-4). Whether the VP precursors are properly sorted and processed remains to be determined, but the presence of VP, NP, and GP immunoreactivity in axons projecting toward the neural lobe of di/di rats (2,3,8) suggests that this may be the case.…”

Section: Resultsmentioning

confidence: 99%

“…These mutations are generally thought to be introduced during mitosis (1). However, the detection of solitary magnocellular neurons with revertant phenotype in the homozygous diabetes insipidus (di/di) Brattleboro rat (2)(3)(4) suggested that post-mitotic cells may also be subjected to mutagenesis. Thus, the di/di rat may serve as a unique model to delineate genomic alterations in nondividing cells.…”

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confidence: 99%

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Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.

Evans

Kleij

Sonnemans

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in DNA underlie , inherited pa , and aging and are generally thght to be mtroduced during melosis and mitosis. Here we report that in post-mitotic neurons spefcfiameit mutations occur at hih fequency. These mutations were identifi in vfastranscripts in e neurons of the homozygous B tleboro rat and predominantly consist of a GA deletion in GAGAG 6059The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.

Evans

Kleij

Sonnemans

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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“…neurons with the di/+ phenotype in the homozygous di/di rat. The age-dependent increase of the number of GP cells most probably explains the difference in the number of these cells reported in the literature (4,5). The absence of GPpositive cells in the suprachiasmatic nucleus need not disagree with the proposed model of gene conversion, since the latter event probably depends on the physical status of the DNA, particularly in regard to chromatin structure: levels of DNA repair have been linked to transcriptional activity- (19).…”

Section: Discussionmentioning

confidence: 98%

“…As a consequence intracellular processing and axonal transport toward the neural lobe ofthe mutant precursor are blocked. Paradoxically, a small number of solitary hypothalamic neurons seems to express wild-type VP gene products that are transported toward the neural lobe (3)(4)(5). To explain these results, an intrachromosomal gene conversion between the homologous exons of the VP and oxytocin (OT) genes has been proposed (6).…”

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confidence: 99%

Age-related development of a heterozygous phenotype in solitary neurons of the homozygous Brattleboro rat.

Leeuwen

Beek²,

Seger³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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A single-base deletion in the single-copy vasopressin gene is the cause of diabetes insipidus in the homozygous Brattleboro rat (di/di). It results in the synthesis of an altered vasopressin precursor of which the axonal transport is blocked. Paradoxically, a small number of solitary hypothalamic neurons displays all the immunoreactivities of the wildtype vasopressin precursor (i.e., vasopressin, neurophysin, and a glycopeptide). In the present paper we provide evidence that these neurons have undergone a switch to a genuine heterozygous (di/+) phenotype; i.e., they contain the immunoreactivities of both the wild-type and the mutated vasopressin precursors. In the neural lobe, glycopeptide fibers are also present, showing that axonal transport of the wild-type precursor is restored. Moreover, the number of neurons displaying this di/+ phenotype increases markedly and in a linear way (from 0.1% up to 3% of the vasopressin cells) with age. These findings indicate that after mitotic division has ceased, genomic alterations occur in somatic neurons in vivo. The molecular event generating the di/+ phenotype in the di/di animal could involve a somatic intrachromosomal gene conversion between the homologous exons of the vasopressin and the related oxytocin genes.Since its discovery in 1961 the diabetes insipidus Brattleboro rat (phenotype, di/di) with impaired vasopressin (VP) synthesis has become an extremely useful model for many disciplines to study hypothalamic diabetes insipidus and to clarify problems related to the physiology ofVP (1). The di/di rat exhibits a recessively inherited hypothalamic diabetes insipidus due to a single-base deletion in the unique VP gene (2). This point mutation results in the synthesis of an altered VP precursor whose C-terminal glycopeptide (GP) moiety, because of a frame-shift, is replaced by a nonglycosylated amino acid sequence (2). As a consequence intracellular processing and axonal transport toward the neural lobe ofthe mutant precursor are blocked. Paradoxically, a small number of solitary hypothalamic neurons seems to express wild-type VP gene products that are transported toward the neural lobe (3-5). To explain these results, an intrachromosomal gene conversion between the homologous exons of the VP and oxytocin (OT) genes has been proposed (6). To (termed, di/+) and that the number of these neurons increases linearly with age. The findings imply that genomic alterations occur after mitotic division has ceased and are compatible with the intrachromosomal gene conversion within the VP/OT gene locus. MATERIALS AND METHODSAnimals and Fixation. Male and female di/di Brattleboro rats of 18 days to 79 weeks of age were obtained from Harlan (Zeist, The Netherlands) or homebred. They were individually checked for water consumption and diuresis. The animals were anaesthetized with Nembutal (60 mg/kg, i.p.) and perfused intracardially with 0.9% NaCl (shortly) and then with 0.1 M sodium phosphate-buffered 4% (wt/vol) paraformaldehyde (pH 7.4) and pieces of tissue then wer...

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“…Early immunohistochemical studies revealed VPir cells in the paraventricular, supraoptic, and suprachiasmatic nuclei (Swaab and Pool, 1975;Swaab et al, 1975a,b;. More recent immunohistochemical studies revealed immunoreactivity for VP (or for epitopes on peptides in the VP prohormone) in neuronal perikarya within the basal septal region and the magnocellular basal forebrain, including the horizontal limb of the diagonal band of Broca, bed nucleus of the stria terminalis, medial amygdaloid nucleus, dorsomedial hypothalamic nucleus, and locus coeruleus De Vries et al, 1985;Sofroniew, 1985;van Leeuwen et al, 1986;Ulfig et al, 1990).…”

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confidence: 99%

Neuroanatomical distribution of vasotocin in a urodele amphibian (Taricha granulosa) revealed by immunohistochemical and in situ hybridization techniques

et al. 1997

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Immunohistochemical and in situ hybridization techniques were used to investigate the neuroanatomical distribution of arginine vasotocin-like systems in the roughskin newt (Taricha granulosa). Vasotocin-like-immunoreactive neuronal cell bodies were identified that, based on topographical position, most likely, are homologous to groups of vasopressin-immunoreactive neuronal cell bodies described in mammals, including those in the bed nucleus of the stria terminalis, medial amygdala, basal septal region, magnocellular basal forebrain-including the horizontal limb of the diagonal band of Broca, paraventricular and supraoptic nuclei, suprachiasmatic nucleus, and dorsomedial hypothalamic nucleus. Several additional vasotocin-like-immunoreactive cell groups were observed in the forebrain and brainstem regions; these observations are compared with previous studies of vasotocin- and vasopressin-like systems in vertebrates. Arginine vasotocin-like-immunoreactive fibers and presumed terminals also were widely distributed with high densities in the basal limbic forebrain, the ventral preoptic and hypothalamic regions, and the brainstem ventromedial tegmentum. Based on in situ hybridization studies with synthetic oligonucleotide probes for vasotocin and the related neuropeptide mesotocin, as well as double-labeling studies with combined immunohistochemistry and in situ hybridization, we conclude that the vasotocin immunohistochemical procedures used identify vasotocin-like, but not mesotocin-like, elements in the brain of T. granulosa. The distribution of arginine vasotocin-like systems in T. granulosa is greater than the distribution previously reported for any other single vertebrate species; however, it is consistent with an emerging pattern of distribution of vasotocin- and vasopressin-like peptides in vertebrates. Complexity in the vasotocinergic system adds further support to the conclusion that this peptide regulates multiple neurophysiological and neuroendocrinological functions.

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Propressophysin is present in neurones at multiple sites in wistar and homozygous brattleboro rat brain

Cited by 21 publications

References 30 publications

Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.

Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.

Age-related development of a heterozygous phenotype in solitary neurons of the homozygous Brattleboro rat.

Neuroanatomical distribution of vasotocin in a urodele amphibian (Taricha granulosa) revealed by immunohistochemical and in situ hybridization techniques

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