Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S]
Intestinal apolipoprotein B (apoB) mRNA undergoes C-to-U editing, mediated by the catalytic deaminase apobec-1, which results in translation of apoB48. Apobec1−/− mice produce only apoB100 and secrete larger chylomicron particles than those observed in wild-type (WT) mice. Here we show that transgen...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-12-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520417997 |
| _version_ | 1830486980726620160 |
|---|---|
| author | Valerie Blanc Yan Xie Jianyang Luo Susan Kennedy Nicholas O. Davidson |
| author_facet | Valerie Blanc Yan Xie Jianyang Luo Susan Kennedy Nicholas O. Davidson |
| author_sort | Valerie Blanc |
| collection | DOAJ |
| description | Intestinal apolipoprotein B (apoB) mRNA undergoes C-to-U editing, mediated by the catalytic deaminase apobec-1, which results in translation of apoB48. Apobec1−/− mice produce only apoB100 and secrete larger chylomicron particles than those observed in wild-type (WT) mice. Here we show that transgenic rescue of intestinal apobec-1 expression (Apobec1Int/O) restores C-to-U RNA editing of apoB mRNA in vivo, including the canonical site at position 6666 and also at approximately 20 other newly identified downstream sites present in WT mice. The small intestine of Apobec1Int/O mice produces only apoB48, and the liver produces only apoB100. Serum chylomicron particles were smaller in Apobec1Int/O mice compared with those from Apobec1−/− mice, and the predominant fraction of serum apoB48 in Apobec1Int/O mice migrated in lipoproteins smaller than chylomicrons, even when these mice were fed a high-fat diet. Because apoB48 arises exclusively from the intestine in Apobec1Int/O mice and intestinal apoB48 synthesis and secretion rates were comparable to WT mice, we were able to infer the major sites of origin of serum apoB48 in WT mice. Our findings imply that less than 25% of serum apoB48 in WT mice arises from the intestine, with the majority originating from the liver. |
| first_indexed | 2024-12-21T18:53:38Z |
| format | Article |
| id | doaj.art-0e76f6f9872c4c9b91dd8fac5660dcf3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:53:38Z |
| publishDate | 2012-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-0e76f6f9872c4c9b91dd8fac5660dcf32022-12-21T18:53:41ZengElsevierJournal of Lipid Research0022-22752012-12-01531226432655Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S]Valerie Blanc0Yan Xie1Jianyang Luo2Susan Kennedy3Nicholas O. Davidson4Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110To whom correspondence should be addressed. e-mail: nod@wustl.edu.; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110Intestinal apolipoprotein B (apoB) mRNA undergoes C-to-U editing, mediated by the catalytic deaminase apobec-1, which results in translation of apoB48. Apobec1−/− mice produce only apoB100 and secrete larger chylomicron particles than those observed in wild-type (WT) mice. Here we show that transgenic rescue of intestinal apobec-1 expression (Apobec1Int/O) restores C-to-U RNA editing of apoB mRNA in vivo, including the canonical site at position 6666 and also at approximately 20 other newly identified downstream sites present in WT mice. The small intestine of Apobec1Int/O mice produces only apoB48, and the liver produces only apoB100. Serum chylomicron particles were smaller in Apobec1Int/O mice compared with those from Apobec1−/− mice, and the predominant fraction of serum apoB48 in Apobec1Int/O mice migrated in lipoproteins smaller than chylomicrons, even when these mice were fed a high-fat diet. Because apoB48 arises exclusively from the intestine in Apobec1Int/O mice and intestinal apoB48 synthesis and secretion rates were comparable to WT mice, we were able to infer the major sites of origin of serum apoB48 in WT mice. Our findings imply that less than 25% of serum apoB48 in WT mice arises from the intestine, with the majority originating from the liver.http://www.sciencedirect.com/science/article/pii/S0022227520417997RNA bindingcytidine deaminasehypereditingapoB48lipoprotein assembly |
| spellingShingle | Valerie Blanc Yan Xie Jianyang Luo Susan Kennedy Nicholas O. Davidson Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S] Journal of Lipid Research RNA binding cytidine deaminase hyperediting apoB48 lipoprotein assembly |
| title | Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S] |
| title_full | Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S] |
| title_fullStr | Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S] |
| title_full_unstemmed | Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S] |
| title_short | Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1−/− mice[S] |
| title_sort | intestine specific expression of apobec 1 rescues apolipoprotein b rna editing and alters chylomicron production in apobec1 mice s |
| topic | RNA binding cytidine deaminase hyperediting apoB48 lipoprotein assembly |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520417997 |
| work_keys_str_mv | AT valerieblanc intestinespecificexpressionofapobec1rescuesapolipoproteinbrnaeditingandalterschylomicronproductioninapobec1mices AT yanxie intestinespecificexpressionofapobec1rescuesapolipoproteinbrnaeditingandalterschylomicronproductioninapobec1mices AT jianyangluo intestinespecificexpressionofapobec1rescuesapolipoproteinbrnaeditingandalterschylomicronproductioninapobec1mices AT susankennedy intestinespecificexpressionofapobec1rescuesapolipoproteinbrnaeditingandalterschylomicronproductioninapobec1mices AT nicholasodavidson intestinespecificexpressionofapobec1rescuesapolipoproteinbrnaeditingandalterschylomicronproductioninapobec1mices |