Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 6 of 6

Publication Record

Connections

Animal model of Sar1b deficiency presents lipid absorption deficits similar to Anderson disease.
Levic DS, Minkel JR, Wang WD, Rybski WM, Melville DB, Knapik EW
(2015) J Mol Med (Berl) 93: 165-76
MeSH Terms: Animals, Animals, Genetically Modified, Body Patterning, Bone and Bones, Brain, Disease Models, Animal, Gastrointestinal Tract, Gene Expression, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Humans, Hypobetalipoproteinemias, Immunohistochemistry, Lipid Metabolism, Malabsorption Syndromes, Monomeric GTP-Binding Proteins, Organogenesis, Phenotype, Zebrafish
Show Abstract · Added February 19, 2015
Anderson disease (ANDD) or chylomicron retention disease (CMRD) is a rare, hereditary lipid malabsorption syndrome associated with mutations in the SAR1B gene that is characterized by failure to thrive and hypocholesterolemia. Although the SAR1B structure has been resolved and its role in formation of coat protein II (COPII)-coated carriers is well established, little is known about the requirement for SAR1B during embryogenesis. To address this question, we have developed a zebrafish model of Sar1b deficiency based on antisense oligonucleotide knockdown. We show that zebrafish sar1b is highly conserved among vertebrates; broadly expressed during development; and enriched in the digestive tract organs, brain, and craniofacial skeleton. Consistent with ANDD symptoms of chylomicron retention, we found that dietary lipids in Sar1b-deficient embryos accumulate in enterocytes. Transgenic expression analysis revealed that Sar1b is required for growth of exocrine pancreas and liver. Furthermore, we found abnormal differentiation and maturation of craniofacial cartilage associated with defects in procollagen II secretion and absence of select, neuroD-positive neurons of the midbrain and hindbrain. The model presented here will help to systematically dissect developmental roles of Sar1b and to discover molecular and cellular mechanisms leading to organ-specific ANDD pathology. Key messages: Sar1b depletion phenotype in zebrafish resembles Anderson disease deficits. Sar1b deficiency results in multi-organ developmental deficits. Sar1b is required for dietary cholesterol uptake into enterocytes.
1 Communities
1 Members
0 Resources
19 MeSH Terms
Identification and characterization of truncated forms of apolipoprotein B in hypobetalipoproteinemia.
Young SG, Krul ES, McCormick S, Farese RV, Linton MF
(1996) Methods Enzymol 263: 120-45
MeSH Terms: Animals, Apolipoproteins B, Blotting, Western, Cell Line, Transformed, Centrifugation, Density Gradient, Chromatography, Chromatography, Gel, DNA, Complementary, Electrophoresis, Polyacrylamide Gel, Genetic Vectors, Heparin, Humans, Hypobetalipoproteinemias, Lipoproteins, HDL, Molecular Weight, Mutation, Recombinant Fusion Proteins, Silver Staining, Transfection
Added May 27, 2014
0 Communities
1 Members
0 Resources
19 MeSH Terms
Familial hypobetalipoproteinemia.
Linton MF, Farese RV, Young SG
(1993) J Lipid Res 34: 521-41
MeSH Terms: Apolipoproteins, Apolipoproteins B, Humans, Hypobetalipoproteinemias, Lipoproteins, Lipoproteins, LDL, Mutation, Phenotype
Added May 27, 2014
0 Communities
1 Members
0 Resources
8 MeSH Terms
Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length.
Young SG, Pullinger CR, Zysow BR, Hofmann-Radvani H, Linton MF, Farese RV, Terdiman JF, Snyder SM, Grundy SM, Vega GL
(1993) J Lipid Res 34: 501-7
MeSH Terms: Adult, Aged, Apolipoproteins B, Base Sequence, Cholesterol, Female, Frameshift Mutation, Humans, Hypobetalipoproteinemias, Lipoproteins, VLDL, Male, Middle Aged, Molecular Sequence Data, Mutation
Show Abstract · Added May 27, 2014
Familial hypobetalipoproteinemia can be caused by mutations in the apolipoprotein (apo)B gene that interfere with the translation of a full-length apoB molecule. Frequently, a truncated apoB molecule can be detected in the plasma lipoproteins of affected subjects. In this report, we characterize four different apoB gene mutations causing hypobetalipoproteinemia that are associated with the synthesis of truncated apoB proteins. Two of the mutations are nonsense mutations caused by single nucleotide substitutions; these mutations are associated with the production of apoB-32.5 (1473 amino acids) and apoB-82 (3733 amino acids). The other two mutations are single nucleotide deletions (of apoB cDNA nucleotides 7295 and 7359, respectively). The altered reading frames created by these different frameshift mutations terminated with the same stop codon, and both therefore yielded a truncated protein of identical size: apoB-52.8 (2395 amino acids). The two apoB-52.8 proteins differ, however, in the number of novel carboxyl-terminal amino acids introduced by the frameshift. The buoyant density of lipoproteins containing the truncated apoBs was inversely related to the length of the truncated apoB. ApoB-32.5 was present only in high density lipoproteins (HDL) and the d > 1.21 g/ml fraction, whereas apoB-82 was present almost exclusively in very low density lipoproteins (VLDL). ApoB-52.8 was present primarily in VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL); trace amounts were observed in the HDL.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Apolipoprotein B gene mutations affecting cholesterol levels.
Farese RV, Linton MF, Young SG
(1992) J Intern Med 231: 643-52
MeSH Terms: Apolipoproteins B, Cholesterol, Gene Expression Regulation, Genetic Variation, Humans, Hypobetalipoproteinemias, Mutation
Show Abstract · Added May 27, 2014
In the past 5 years, many different mutations in the apolipoprotein (apo) B gene have been described that affect plasma cholesterol levels. More than 20 different mutations in the apoB gene have been shown to cause familial hypobetalipoproteinaemia, a condition characterized by abnormally low plasma concentrations of apoB and LDL cholesterol. Almost all of the mutations are nonsense or frameshift mutations that interfere with the translation of a full-length apoB100 molecule. Many, but not all, of these apoB gene mutations result in the synthesis of a truncated species of apoB that can be detected within the plasma lipoproteins. Familial hypobetalipoproteinaemia heterozygotes are almost always asymptomatic and have LDL cholesterol levels about one-quarter to one-third of those of unaffected family members. Several homozygotes and compound heterozygotes for familial hypobetalipoproteinaemia have been described. In these individuals, the LDL cholesterol levels are extremely low, usually less than 5 or 10 mg dl-1, and the clinical phenotype is variable, ranging from completely asymptomatic to severe problems related to intestinal fat malabsorption. One missense mutation in the apoB gene (an Arg----Gln substitution at apoB amino acid 3500) is associated with very poor binding of apoB100 to the cellular LDL receptor. This syndrome has been designated familial defective apolipoprotein B (FDB). The amino-acid substitution at residue 3500 delays the clearance of LDL from the plasma and results in hypercholesterolaemia. In some Western populations, the frequency of FDB heterozygotes appears to be as high as 1 in 500 individuals.
0 Communities
1 Members
0 Resources
7 MeSH Terms
Reading-frame restoration with an apolipoprotein B gene frameshift mutation.
Linton MF, Pierotti V, Young SG
(1992) Proc Natl Acad Sci U S A 89: 11431-5
MeSH Terms: Alleles, Amino Acid Sequence, Animals, Apolipoproteins B, Base Sequence, DNA, Frameshift Mutation, Gene Expression, Genes, Humans, Hypobetalipoproteinemias, In Vitro Techniques, Molecular Sequence Data, Pedigree, RNA, Messenger, Rats, Transcription, Genetic, Tumor Cells, Cultured
Show Abstract · Added May 27, 2014
We examined a mutant human apolipoprotein B (apoB) allele that causes hypobetalipoproteinemia and has a single cytosine deletion in exon 26. This frameshift mutation was associated with the synthesis of a truncated apoB protein of the predicted size; however, studies in human subjects and minigene expression studies in cultured cells indicated that the mutant allele also yielded a full-length apoB protein. The 1-base-pair deletion in the mutant apoB allele created a stretch of eight consecutive adenines. To understand the mechanism whereby the mutant apoB allele yielded a full-length apoB protein, the cDNA from cells transfected with the mutant apoB minigene expression vector was examined. Splicing of the mRNA was normal; however, 11% of the cDNA clones had an additional adenine within the stretch of eight adenines, yielding nine consecutive adenines. The insertion of the extra adenine, presumably during apoB gene transcription, is predicted to restore the correct apoB reading frame, thereby permitting the synthesis of a full-length apoB protein.
0 Communities
1 Members
0 Resources
18 MeSH Terms