ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : The hph-1 mouse is characterized by low levelsof GTP cyclohydrolase I (GTPCH) and tetrahydrobiopterin. A quantitativedouble-lable in situ hybridization technique was used to examine CNS GTPCHmRNA expression within serotonin, dopamine, and norepinephrine neurons of maleand female wild-type and hph-1 mice. In wild-type male and femaleanimals the highest levels of GTPCH mRNA expression were observed withinserotonin neurons, followed by norepinephrine and then dopamine neurons.Wild-type female animals were found to express lower levels of GTPCH mRNA ineach cell type when compared with levels seen in wild-type males. GTPCH mRNAabundance in all three cell types was lower in hph-1 male than inwild-type male mice, with the greatest reduction in serotonin neurons. GTPCHmRNA levels were also lower in hph-1 female than in wild-type femalemice, again with the greatest reduction occurring in serotonin neurons.Comparison of hph-1 male and hph-1 female mice revealed thatthe sex-linked difference in GTPCH mRNA expression observed in wild-typeneurons was only present within female dopamine neurons. Overall, theseresults indicate that not only are basal levels of GTPCH mRNA expressionheterogeneous across wild-type murine monoamine cell types but that geneexpression is also modified in a sex-linked and cell-specific fashion by thehph-1 gene locus. The hph-1 mutation does not lie within theGT-PCH mRNA coding region. The 5′ flanking region of the GTPCH gene wascloned and sequenced and shown to be identical for both wild-type andhph-1 genomic DNA. Transient transfection assays performed in PC12cells demonstrated that this 5′ flanking region was sufficient toinitiate transcription of a luciferase reporter gene. Although thehph-1 mutation does not lie within the 5′ flanking region of the GTPCH gene, this region of the gene can function as a core promoter and is thus crucial to the control of GTPCH gene expression.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720757.x
