Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the hypothalamus die at approximately E12.5. All homozygous mutants suffered mortality within 10 days after birth, possibly because of a complete deficiency of these neurons in the hypothalamus. Although neither developmental nor histological abnormalities were observed in heterozygous mice, the levels of expression of vasopressin and oxytocin in the hypothalamus of these animals were half these of wild-type mice. These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus.
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PMID:The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. 854 55

The bHLH-PAS transcription factor SIM1 is expressed during the development of the hypothalamic-pituitary axis in three hypothalamic nuclei: the paraventricular nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic nucleus (SON). To investigate Sim1 function in the hypothalamus, we produced mice carrying a null allele of Sim1 by gene targeting. Homozygous mutant mice die shortly after birth. Histological analysis shows that the PVN and the SON of these mice are hypocellular. At least five distinct types of secretory neurons, identified by the expression of oxytocin, vasopressin, thyrotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin, are absent in the mutant PVN, aPV, and SON. Moreover, we show that SIM1 controls the development of these secretory neurons at the final stages of their differentiation. A subset of these neuronal lineages in the PVN/SON are also missing in mice bearing a mutation in the POU transcription factor BRN2. We provide evidence that, during development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails to express Brn2. Our results strongly indicate that SIM1 functions upstream to maintain Brn2 expression, which in turn directs the terminal differentiation of specific neuroendocrine lineages within the PVN/SON.
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PMID:Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. 978

We have used an over-expression strategy to test the hypothesis that the Class III POU transcription factor Brn2 is rate limiting in the control of the level of expression of the vasopressin (VP) gene in the paraventricular nucleus of the rat hypothalamus. Knockout studies in mice have suggested that Brn2 may contribute to the control of the level of VP gene expression in the adult hypothalamus. However, we show here that in heterologous cell lines, Brn2 transactivates neither the proximal promoter of the rat VP gene, nor a novel reporter construct consisting of the rat VP structural gene and 3 and 2 kbp of upstream and downstream flanking sequences. We hypothesised that this maybe due either to the lack of cis-acting elements within the confines of the reporter vectors used, or to the absence in heterologous cells, of factors required for Brn2 activity. As no cell lines exist that correspond to VP neurons, we devised an adenoviral vector delivery strategy that enabled efficient over-expression of Brn2 in the paraventricular nucleus of the intact rat. Localised over-expression of Brn2 had no effect on VP hnRNA levels. Neither did we detect corticotrophin releasing factor (CRF) mRNA up-regulation by Brn2 over-expression in vivo. This was unexpected as Brn2 transactivates the proximal CRF promoter in vitro. Whilst Brn2 is required for the development of the hypothalamic structures that express VP and CRF, these data suggest that this transcription factor is not required, or is not rate limiting, for expression in the adult.
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PMID:Adenoviral-mediated over-expression of Brn2 in the rat paraventricular nucleus: no effect on vasopressin or corticotrophin releasing factor RNA levels. 1264 9