title: Targeted disruption of the peroxisomal thiolase B gene in mouse: a new model to study disorders related to peroxisomal lipid metabolism.
abstract: The peroxisomal beta-oxidation system consists of four steps catalysed by three enzymes: acyl-CoA oxidase, 3-hydroxyacyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase. In humans, thiolase activity is encoded by one gene, whereas in rodents, three enzymes encoded by three distinct genes (i.e. thiolase A, thiolase B and SCP2/thiolase) catalyse the thiolase activity. So far, acyl-CoA oxidase- and multifunctional enzyme-deficient patients have been identified and knock-out mice for these genes have been produced. Conversely, no isolated thiolase-deficient patient has been found, and no thiolase (A or B)-deficient mice have been generated. Hence, to better understand the cause of isolated human thiolase deficiency, we disrupted the catalytic site of the mouse thiolase B by homologous recombination in order to analyse the phenotype of these thiolase B-deficient mice. Mice, made homozygous for the mutation, lack expression of thiolase B mRNA and are viable, fertile and healthy at birth. They exhibit no detectable phenotype defects and no compensation, rather a slight decrease in other peroxisomal thiolase (thiolase A and SCPx) mRNAs, was found.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire (GDR-CNRS n(o) 2583), Université de Bourgogne, 6, bd Gabriel, 21000 Dijon, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Chevillard
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Clémencet
authors.forename: Norbert
authors.initials: N
authors.lastname: Latruffe
authors.forename: Valérie
authors.initials: V
authors.lastname: Nicolas-Francès
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018901:Peroxisomal Disorders / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D013329:Structure-Activity Relationship
chemical_list: D012333:RNA, Messenger; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; C486234:Acaa1b protein, mouse; D000102:Acetyl-CoA C-Acyltransferase; C065185:D-3-hydroxyacyl CoA dehydratase; D006836:Hydro-Lyases