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

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11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)72-87
Number of pages15
JournalMolecular and Cellular Neuroscience
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2002

Keywords

  • central nervous system
  • messenger RNA expression
  • in-situ hybridization
  • neurokinin A
  • spinal chord
  • rat brain
  • mammary gland
  • receptor
  • neurons
  • localization

Cite this

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title = "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",
abstract = "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.",
keywords = "central nervous system, messenger RNA expression, in-situ hybridization, neurokinin A, spinal chord, rat brain, mammary gland, receptor, neurons, localization",
author = "Alasdair MacKenzie and J. Quinn",
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AU - Quinn, J.

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AB - 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.

KW - central nervous system

KW - messenger RNA expression

KW - in-situ hybridization

KW - neurokinin A

KW - spinal chord

KW - rat brain

KW - mammary gland

KW - receptor

KW - neurons

KW - localization

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