APOLIPOPROTEIN-B RNA EDITING ENZYME-DEFICIENT MICE ARE VIABLE DESPITEALTERATIONS IN LIPOPROTEIN METABOLISM

RNA editing in the nucleus of higher eukaryotes results in subtle chan ges to the RNA sequence, with the ability to effect dramatic changes i n biological function. The first example to be described and among the best characterized, is the cytidine-to-uridine editing of apolipoprot ein B (apo-B) RNA. The editing of apo-B RNA is mediated by a novel cyt idine deaminase, apobec-1, which has acquired the ability to bind RNA. The stop translation codon generated by the editing of apo-B RNA trun cates the full-length apo-B100 to form apo-B48. The recent observation s of tumor formation In Apobec-1 transgenic animals, together with the fact that Apobec-1 is expressed in numerous tissues lacking apo-B, ra ises the issue of whether this enzyme is essential for a variety of po sttranscriptional editing events, To directly test this, mice were cre ated with a null mutation in Apobec-1 using homologous recombination i n embryonic stem cells. Mice, homozygous for this mutation, were viabl e and made apo-B100 but not apo-B48. The null animals were fertile, an d a variety of histological, behavioral, and morphological analyses re vealed no phenotype other than abnormalities in lipoprotein metabolism , which included an increased tow density lipoprotein fraction and a r eduction in high density lipoprotein cholesterol. These studies demons trate that neither apobec-1 nor apo-B48 is essential for viability and suggest that the major role of apobec-1 may be confined to the modula tion of lipid transport.