Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism.
RNA editing in the nucleus of higher eukaryotes results in subtle changes to the RNA sequence, with the ability to effect dramatic changes in biological function. The first example to be described and among the best characterized, is the cytidine-to-uridine editing of apolipoprotein B (apo-B) RNA. The editing of apo-B RNA is mediated by a novel cytidine deaminase, apobec-1, which has acquired the ability to bind RNA. The stop translation codon generated by the editing of apo-B RNA truncates the full-length apo-B100 to form apo-B48. The recent observations of tumor formation in Apobec-1 transgenic animals, together with the fact that Apobec-1 is expressed in numerous tissues lacking apo-B, raises the issue of whether this enzyme is essential for a variety of posttranscriptional editing events. To directly test this, mice were created with a null mutation in Apobec-1 using homologous recombination in embryonic stem cells. Mice, homozygous for this mutation, were viable and made apo-B100 but not apo-B48. The null animals were fertile, and a variety of histological, behavioral, and morphological analyses revealed no phenotype other than abnormalities in lipoprotein metabolism, which included an increased low density lipoprotein fraction and a reduction in high density lipoprotein cholesterol. These studies demonstrate 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 modulation of lipid transport.
Morrison
J R
JR
Department of Molecular Medicine, Medical Research Council, Hammersmith Hospital, London, United Kingdom.
Pászty
C
C
Stevens
M E
ME
Hughes
S D
SD
Forte
T
T
Scott
J
J
Rubin
E M
EM
D000071479:APOBEC-1 Deaminase; D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis*; D001483:Base Sequence; D008076:Cholesterol, HDL / Q000097:blood; D002914:Chylomicrons / Q000378:metabolism; D003314:Corn Oil; D003562:Cytidine; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D017931:DNA Primers; D004041:Dietary Fats; D015870:Gene Expression; D008077:Lipoproteins, LDL / Q000097:blood; D018782:Maze Learning; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017393:RNA Editing / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D013234:Stem Cells; D014280:Triglycerides / Q000097:blood; D014529:Uridine; D014801:Vitamin A / Q000494:pharmacology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D002914:Chylomicrons; D017931:DNA Primers; D004041:Dietary Fats; D008077:Lipoproteins, LDL; D014280:Triglycerides; D014801:Vitamin A; D003562:Cytidine; D003314:Corn Oil; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase; D014529:Uridine