title: Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48.
abstract: A site-specific C to U editing reaction modifies nuclear apolipoprotein B100 (apoB100) mRNA, producing apolipoprotein B48 in the mammalian small intestine. This reaction is mediated by a multicomponent enzyme complex, which contains a catalytic subunit, Apobec-1. We have used gene targeting to disrupt mouse apobec-1 in order to establish its requisite importance in apoB mRNA editing and also, in view of its widespread tissue distribution in rodents, as a preliminary indication of other potential roles. Both heterozygous (apobec-1+/-) and homozygous (apobec-1-/-) gene-targeted mice appear healthy and fertile with no alterations in serum cholesterol or triglyceride concentrations. The apobec-1+/- mice demonstrated reduced levels of hepatic apoB mRNA editing. By contrast, levels of small intestinal apoB mRNA editing were indistinguishable in wild-type and apobec-1+/- animals, suggesting that Apobec-1 is expressed in limited quantities in the liver but not in the small intestine. The apobec-1-/- mice lacked detectable levels of Apobec-1 mRNA, expressed only unedited apoB mRNA in all tissues, and contained no apoB48 in their serum, demonstrating that there is no functional duplication of this gene.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: S G
authors.initials: SG
authors.lastname: Young
authors.forename: R V
authors.initials: RV
authors.lastname: Farese
authors.forename: J
authors.initials: J
authors.lastname: Ng
authors.forename: E
authors.initials: E
authors.lastname: Sande
authors.forename: C
authors.initials: C
authors.lastname: Warburton
authors.forename: L M
authors.initials: LM
authors.lastname: Powell-Braxton
authors.forename: N O
authors.initials: NO
authors.lastname: Davidson
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000235:genetics*; D001161:Arteriosclerosis / Q000209:etiology; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017393:RNA Editing; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D017931:DNA Primers; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase