Phenobarbital induction of aldehyde dehydrogenase type 2 mRNA in mouse liver: a candidate region on chromosome 7 for a putative regulatory gene.
Phenobarbital (PB) strongly induces in the liver the expression of many genes encoding detoxication enzymes, such as the aldehyde dehydrogenase type 2 in the mouse (Aldh2). With the aim of identifying genes involved in this response, we have undertaken an approach based on a genetic analysis in mice. In a previous report, the genetic analysis of both the C57BL/6J (B6) x DBA/2J (D2) F1 and the (F1 x F1) F2 led us to the hypothesis that Aldh2 responsiveness to PB was under the control of one major locus independent of the structural gene. In the present study, the genetic analysis of the inducibility by PB of Aldh2 in the backcross population B6D2F1 x D2 has allowed us to confirm the involvement of a major regulatory gene in this mechanism. By searching for genetic linkage between this locus and a series of microsatellites DNA markers, we obtained indicative evidence for a region on chromosome 7, which may carry this gene.
Marc
N
N
INSERM U456, Faculté de Pharmacie, 2 av. Léon Bernard, 35043 Rennes, France.
Fautrel
A
A
Damon
M
M
Guillouzo
A
A
Corcos
L
L
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004790:Enzyme Induction; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005838:Genotype; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018895:Microsatellite Repeats; D010634:Phenobarbital / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D010634:Phenobarbital