PMID- 15233746
OWN - NLM
STAT- MEDLINE
DCOM- 20040930
LR  - 20141120
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 20
IP  - 2
DP  - 2004 Jul
TI  - Analysis of the murine 5-HT receptor gene promoter in vitro and in vivo.
PG  - 363-74
AB  - The expression level of the 5-HT(1A) receptor gene (htr1a) in the central nervous 
      system (CNS) is implicated in the aetiology and treatment of anxiety disorders 
      and depression. Previous studies of the murine htr1a have revealed that its 
      proximal promoter is GC rich and TATA-less. Several functional transcription 
      factor binding sites, including MAZ and SP1 recognition sequences, have been 
      identified. To further analyse the promoter of this receptor gene, additional 
      upstream sequence information extending to -5.5 kb of the murine htr1a was 
      generated and promoter fragments extending to -20 kb were analysed for activity 
      in cell culture and transgenic animals. Promoter fragments greater than 4.5 kb in 
      length were active in 5-HT(1A) receptor mRNA positive cells and inactive in 
      5-HT(1A) receptor mRNA negative cells. Smaller fragments were not able to confer 
      this specificity. In agreement, using additive transgenesis to drive LacZ 
      expression in vivo, CNS specific reporter gene expression was found with these 
      longer constructs. Transgene expression in the 4.5- and 20-kb mouse lines 
      resembled the endogenous htr1a expression pattern, whereas the 5.5-kb mouse lines 
      surprisingly revealed strongly reduced expression. None of the three constructs 
      was prone to confer ectopic expression, however, variation of expression between 
      the transgenic lines was observed. Using colocalization studies we analysed the 
      degree of concurrence of transgenic and endogenous htr1a expression brought about 
      by these three different constructs. The highest degrees of colocalization were 
      observed in mice harbouring the 20-kb construct, suggesting a large promoter 
      fragment is required to faithfully direct transgene expression in a 5-HT(1A) 
      receptor like pattern.
FAU - Ansorge, Mark
AU  - Ansorge M
AD  - Institute for Pharmacology and Toxicology, Charite University Hospital, 
      Dorotheenstrasse 94, D 10117 Berlin, Germany.
FAU - Tanneberger, Cornelia
AU  - Tanneberger C
FAU - Davies, Benjamin
AU  - Davies B
FAU - Theuring, Franz
AU  - Theuring F
FAU - Kusserow, Heike
AU  - Kusserow H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Cell Line
MH  - Central Nervous System/chemistry/metabolism/*physiology
MH  - *Gene Expression Regulation
MH  - Genes, Reporter/genetics
MH  - In Situ Hybridization
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuroblastoma
MH  - Promoter Regions, Genetic/*genetics
MH  - Receptor, Serotonin, 5-HT1A/*genetics/metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Transgenes/physiology
MH  - beta-Galactosidase/analysis/biosynthesis
EDAT- 2004/07/06 05:00
MHDA- 2004/10/01 05:00
CRDT- 2004/07/06 05:00
PHST- 2004/07/06 05:00 [pubmed]
PHST- 2004/10/01 05:00 [medline]
PHST- 2004/07/06 05:00 [entrez]
AID - EJN3472 [pii]
AID - 10.1111/j.1460-9568.2004.03472.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2004 Jul;20(2):363-74. doi: 10.1111/j.1460-9568.2004.03472.x.