Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toward an understanding of the mechanisms controlling Preprotachykinin-A (PPTA) transcription, we introduced a 380-kb human yeast artificial chromosome containing the PPTA gene tagged with the beta-galactosidase gene into transgenic mice. This resulted in a pattern of LacZ expression in the central nervous system (CNS) remarkably similar to that reported for PPTA mRNA in the rat. However, the human gene drove expression in areas of the mouse CNS not associated with strong PPTA expression in rodents but which have been shown to express PPTA in the human. This study clearly demonstrates the high degree of conservation of the mechanisms involved in PPTA transcription that has occurred throughout 100 million of divergent human and rodent evolution. This study also defines the maximum linear extent of the human PPT-A promoter. We believe these findings constitute the removal of a significant obstacle in studying the transcriptional regulation of the human PPTA gene in vivo.
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PMID:The human preprotachykinin-A gene promoter has been highly conserved and can drive human-like marker gene expression in the adult mouse CNS. 1108 23

We have produced a yeast artificial chromosome (YAC) transgenic model containing the human preprotachykinin-A gene (hPPTA) that can drive appropriate expression of beta-galactosidase within the adult mouse brain. Here, we investigate its embryonic expression to assess the transcriptional regulation of the PPTA gene during the development of several neural pathways later affected by disease in humans. We demonstrate that the human PPTA gene regulatory region is active in appropriate areas of the developing brain at significantly earlier time points than has been previously reported. Furthermore, despite replacement of most of the 3' untranslated region by the marker gene cassette, the modified human YAC is able to express substance P (SP) on a murine SP/NKA(-/-) background. This transgenic model, in addition to being valuable in examining the hPPTA regulatory region, will also prove to be important in exploring the downstream function of the gene in the adult and the embryo brain.
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PMID:A yeast artificial chromosome containing the human preprotachykinin-A gene expresses substance P in mice and drives appropriate marker-gene expression during early brain embryogenesis. 1181 99

The rat preprotachykinin-A gene, which encodes substance P, is expressed in response to nerve growth factor in a subpopulation of dorsal root ganglion sensory neurons. To investigate mechanisms regulating preprotachykinin-A transcription, we transfected adult rat sensory neurons in culture by microinjection of plasmids containing genomic DNA sequences linked to a lacZ (beta-galactosidase) reporter gene. Expression of beta-galactosidase was seen in 10-15% of neurons receiving injections of prPPT-betaGAL1, which contained the preprotachykinin transcription start site and 3356 bp of 5'-flanking DNA. Deletion analysis showed that expression was directed by 865 bp lying immediately upstream of the transcription start site. Extension of the prPPT-betaGAL1 sequence to include the first intron of preprotachykinin increased beta-galactosidase two- to threefold. Functional promoter and enhancer sequences from the rat prolactin gene failed to direct expression in sensory neurons, indicating neuronal selectivity for preprotachykinin sequences. Expression of prPPT-betaGAL1, measured relative to a construct containing the Rous sarcoma virus promoter, was approximately fivefold higher in neurons than in nonneuronal cells. This suggests selectivity by preprotachykinin 5'-flanking sequences for neuronal expression. However, prPPT-betaGAL1 expression was not restricted to the neuronal subpopulation containing immunoreactive substance P nor was it dependent upon nerve growth factor. Therefore, it does not share all the characteristics of endogenous preprotachykinin expression implying the need for additional regulatory sequences or the involvement of post-transcriptional regulation. Our results show that transfection of differentiated neurons in culture by microinjection has considerable potential in studies of neuron-specific gene expression.
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PMID:5'-flanking sequences from the rat preprotachykinin gene direct high-level expression of a reporter gene in adult rat sensory neurons transfected in culture by microinjection. 1991 19


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