Molecular cloning, gene structure and expression profile of two mouse peroxisomal 3-ketoacyl-CoA thiolase genes.
BACKGROUND
In rats, two peroxisomal 3-ketoacyl-CoA thiolase genes (A and B) have been cloned, whereas only one thiolase gene is found in humans. The aim of this study was thus to clone the different mouse thiolase genes in order to study both their tissue expression and their associated enzymatic activity.


RESULTS
In this study, we cloned and characterized two mouse peroxisomal 3-ketoacyl-CoA thiolase genes (termed thiolase A and B). Both thiolase A and B genes contain 12 exons and 11 introns. Using RNA extracted from mouse liver, we cloned the two corresponding cDNAs. Thiolase A and B cDNAs possess an open reading frame of 1272 nucleotides encoding a protein of 424 amino acids. In the coding sequence, the two thiolase genes exhibited approximately equal to 97% nucleotide sequence identity and approximately equal to 96% identity at the amino acid level. The tissue-specific expression of the two peroxisomal 3-ketoacyl-CoA thiolase genes was studied in mice. Thiolase A mRNA was mainly expressed in liver and intestine, while thiolase B mRNA essentially exhibited hepatic expression and weaker levels in kidney, intestine and white adipose tissue. Thiolase A and B expressions in the other tissues such as brain or muscle were very low though these tissues were chiefly involved in peroxisomal disorders. At the enzymatic level, thiolase activity was detected in liver, kidney, intestine and white adipose tissue but no significant difference was observed between these four tissues. Moreover, thiolase A and B genes were differently induced in liver of mice treated with fenofibrate.


CONCLUSIONS
Two mouse thiolase genes and cDNAs were cloned. Their corresponding transcripts are mostly expressed in the liver of mice and are differently induced by fenofibrate.
Chevillard
Grégory
G
Laboratoire de Biologie Moléculaire et Cellulaire (GDR-CNRS no 2583), Université de Bourgogne, 6 Bd Gabriel, 21000 Dijon, France. chevillardgreg@yahoo.fr
Clémencet
Marie-Claude
MC
Etienne
Philippe
P
Martin
Pascal
P
Pineau
Thierry
T
Latruffe
Norbert
N
Nicolas-Francès
Valérie
V
D000102:Acetyl-CoA C-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D011345:Fenofibrate / Q000494:pharmacology; D040461:Gene Components; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D020675:Peroxisomes / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
D012333:RNA, Messenger; C486233:Acaa1a protein, mouse; C486234:Acaa1b protein, mouse; D000102:Acetyl-CoA C-Acyltransferase; D011345:Fenofibrate