Functional analysis of the mouse galactose-1-phosphate uridyl transferase (GALT)promoter.
Mol Genet Metab
; 72(1): 31-8, 2001 Jan.
Article
em En
| MEDLINE
| ID: mdl-11161826
ABSTRACT
Galactose-1-phosphate uridyltransferase (GALT) is expressed in most tissues, but the near total absence of catalytic activity in humans with the disease galactosemia leads to specific organ dysfunction, the pathophysiology of which remains an enigma. To characterize the transcriptional regulation of the mouse GALT gene, we isolated and sequenced over 3 kb of a 5'-flanking sequence and functionally characterized the region using in vitro transient transfection and in transgenic mice. A minimal promoter of 145 bp was found to function in both HepG2 cells and NS20Y mouse neuroblastoma cells. The minimal promoter contains regions of homology to the corresponding rat and human GALT genes. In transgenic mice expressing a luciferase transgene under control of a 1.9-kb fragment of the mGALT promoter region, reporter activity was found in most tissues, with higher than expected reporter levels in neonatal brain. To determine if high galactose levels in tissues could induce promoter activity, we bred the mGALTluciferase transgene into a line of mice in which the GALT gene function has been eliminated by homologous recombination. High tissue levels of galactose and metabolites did not induce reporter activity above background. The studies show that GALT transcriptional regulation is complex and not directly induced by substrate levels.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
UTP-Hexose-1-Fosfato Uridililtransferase
/
Regiões Promotoras Genéticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos