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Abetalipoproteinemia - Crossref

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Last Updated: 10 November 2022

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Knockout of the abetalipoproteinemia gene in mice: Reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes

To knock out the mouse MTP gene, we used gene editing. Mttp +/-u2212 mice were reduced in plasma levels of low-density lipoprotein cholesterol and had a 28 percent decrease in plasma apoB100 levels, relative to control mice. The Mttp+/u2212 mice on a high-fat diet had a significant decrease in total plasma cholesterol levels compared to those in Mttp+/+ mice, which were on a high-fat diet. Both the livers of adult Mttp+/u2212 mice and the yolk sacs from Mttp+/-u2212 embryos showed an increase of cytosolic fat. MTP deficiency leads to lethal developmental abnormalities in children, in particular due to the yolk sac's inability to export lipids to the developing embryo.

Source link: https://doi.org/10.1073/pnas.95.15.8686


Regulation of low density lipoprotein receptors by plasma lipoproteins from patients with abetalipoproteinemia.

According to these reports, other lipoprotein particles present in the blood of patients with abetalipoproteinemia may influence LDL receptor activity and cell cholesterol synthesis in this condition. Normal subjects or the high density lipoprotein fraction HDL2 from the plasma of patients with abetalipoproteinemia have down-regulated LDL receptor function, which has effectively reduced LDL receptor synthesis. The cultured human fibroblasts' cultured 125I-LDL from the plasma of patients with abetalipoproteinemia also decreased the binding, internalization, and degradation of 125I-LDL by cultured human fibroblasts. We conclude that lipoproteins present in the HDL2 fraction of plasma from patients with abetalipoproteinemia are potent regulators of LDL receptor function in normal human fibroblasts. These in vitro findings may explain why the in vivo rates of cholesterol synthesis and the number of LDL receptors isolated on freshly isolated cells from patients with abetalipoproteinemia have not increased in vivo.

Source link: https://doi.org/10.1073/pnas.80.11.3475


Hormone changes during the menstrual cycle in abetalipoproteinemia: reduced luteal phase progesterone in a patient with homozygous hypobetalipoproteinemia.

The human corpus luteum's synthesis requires cholesterol, which can be obtained from both local manufacture and uptake of low density lipoproteins. Progesterone synthesis is mainly dependent on LDL and the rate of progesterone production during expansion in a LDL-free media when the corpus luteum is maintained in organ culture, although it is suboptimal.

Source link: https://doi.org/10.1073/pnas.79.21.6685


Abstract 547: A Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of N-terminal β-barrel in Microsomal Triglyceride Transfer Protein Function

Background: Because of associated hepatosteatosis, the use of microsomal triglyceride transfer protein inhibitors is limited to severe hyperlipidemias. Comprehensive knowledge of MTP's structure-function can help develop new molecules that minimize steatosis. Protein disulfide isomerase binding and lipid transfer activity are key to protein disulfide isomerase binding and lipid transfer activity in MTP causing abetalipoproteinemia, according to characterization of mutations in MTP causing abetalipoproteinemia. Methods and Findings: In a 4-month old Turkish male with severe signs of ABL, we discovered a novel missense mutation. Despite the fact that D169V was expressed in the endoplasmic reticulum and collaborated with apoB17, it was unable to bind PDI, transfer lipids, or help with apoB secretion. D169, according to computational modeling, might form an internal salt bridge with K187 and K189. Mutagenesis of these lysines to leucines halted PDI heterodimerization, lipid exchange, and automob silence, which did not have an effect on apoB-binding.

Source link: https://doi.org/10.1161/atvb.35.suppl_1.547


Abstract 232: A Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal ß-Sheet in the Lipid Transfer and ApoB Secretion Activities of Microsomal Triglyceride Transfer Protein

For the formation and concealment of apolipoprotein B-containing lipoproteins, a microsomal triglyceride transfer protein is essential. The central u03b1-helical and C-terminal u03b2-sheet domains in ABL have shown that the lipid transfer activity of MTP and the assembly and concealment of apoB-containing lipoproteins are crucial for the assembly and concealment of apoB-containing lipoproteins. D169 could be an internal salt bridge with K187 and K189, according to computational molecular modeling. Moreover, the mutagenesis of these lysine residues to leucine has stopped the triglyceride transfer and MTP's covertion activities. D169 is undoubtedly involved in an internal salt bridge with K187 and K189, according to the authors. This internal salt bridge in the N-terminal region's disruption has an effect on the MTP molecule's lipid transfer activity, which is visible in the C-terminal region. This salt bridge, although away from the rumored lipid transfer site, may be important in providing structural stability for MTP's lipid transfer activity.

Source link: https://doi.org/10.1161/atvb.34.suppl_1.232


Abstract 398: Loss of Both Phospholipid and Triglyceride Transfer Activities of Microsomal Triglyceride Transfer Protein in Abetalipoproteinemia

Mutations in microsomal triglyceride transfer protein result in abetalipoproteinemia, which is characterized by the lack of plasma Apolipoprotein B -containing lipoproteins. We characterized the consequences of several MTP missense mutations found in ABL patients with respect to their expression, subcellular location, and interaction with Protein Disulfide Isomerase in this research. We found that R540H and N780Y, which are known to be deficient in triglyceride transfer activity, also lack phospholipid transfer capacity. These results show that ABL is correlated with the absence of both triglyceride and phospholipid transfer enzymes in MTP.

Source link: https://doi.org/10.1161/atvb.33.suppl_1.a398


Abstract 192: Characterization of Microsomal Triglyceride Transfer Protein Missense Mutations Found in Abetalipoproteinemia and Hybobetalipoproteinemia Subjects

We describe two new hypolipidemic patients with extremely low plasma triglyceride and apolipoprotein B levels and lipid malabsorption with plasma lipid profiles that are similar to abetalipoproteinemia patients. The R46G had no effect on MTP expression or function, and it had no effect on MTP expression or function, and it also promoted apoB secrecy. As D361E was able to sustain apoB secrecy and transfer lipids, MTP function was vital for MTP operation. On the other hand, the hypolipidemia in the other two patients was not due to MTP dysfunction, not related to MTP dysfunction. Four of the mutations did not influence MTP function in three hypolipidemic patients, according to this review. Therefore, there are likely to exist novel mutations in other genes that result in severe hypogemia and their recognition, as well as novel proteins involved in the synthesis and/or catabolism of plasma lipoproteins.

Source link: https://doi.org/10.1161/atvb.36.suppl_1.192


Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function

Backgroundu2014 The use of microsomal triglyceride transfer protein inhibitors is limited to severe hyperlipidemias due to chronic hyperlipidemia and gastrovascular adverse effects, which can be related to gastropareta. Comprehensive knowledge of MTP's structureu2013function may help design new molecules that minimize steatosis. The central u03b1-helical and C-terminal u03b2-sheet domains are critical for protein disulfide isomerase binding and lipid transfer activity in MTP. Methods and Resultsu2014 We found a novel missense mutation in a 4-month-old Turkish male child with significant signs of abetalipoproteinemia in a 4-month-old Turkish male child. D169 could form an internal salt bridge with K187 and K189, according to computational analysis. U2014 D169V is detrimental because it disrupts an internal salt bridge, contributing to loss of protein disulfide isomerase binding and lipid transfer functions; however, it does not influence apoB binding. According, the MTP's N-terminal domain is also important for its lipid transfer activity.

Source link: https://doi.org/10.1161/circgenetics.115.001106


Abetalipoproteinemia Caused by Maternal Isodisomy of Chromosome 4q Containing an Intron 9 Splice Acceptor Mutation in the Microsomal Triglyceride Transfer Protein Gene

Abstract u2014Uniparental disomy, a rare inheritance of two copies of a single chromosome homolog or a region of a chromosome homolog from one parent, can cause various autosomal recessive diseases. Abetalipoproteinemia is a rare autosomal recessive deficiency of apoB-containing lipoproteins resulting from a microsomal triglyceride transfer protein deficiency. In this research, we identify a patient with ABL as a homozygous intron 9 splice acceptor G-to-A mutation of the transfer protein gene. The MTP gene mutation in this patient caused homozygosity.

Source link: https://doi.org/10.1161/01.atv.19.8.1950

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions