Abstract：
:Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-∆7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral and cognitive defects, with characteristically elevated levels of 7-dehydrocholesterol (7-DHC) in all bodily tissues and fluids. Previous mouse models of SLOS have been hampered by postnatal lethality when Dhcr7 is knocked out globally, while a hypomorphic mouse model showed improvement in the biochemical phenotype with ageing, and did not manifest most other characteristic features of SLOS. We report the generation of a conditional knockout of Dhcr7 (Dhcr7flx/flx), validated by generating a mouse with a liver-specific deletion (Dhcr7L-KO). Phenotypic characterization of liver-specific knockout mice revealed no significant changes in viability, fertility, growth curves, liver architecture, hepatic triglyceride secretion, or parameters of systemic glucose homeostasis. Furthermore, qPCR and RNA-Seq analyses of livers revealed no perturbations in pathways responsible for cholesterol synthesis, either in male or female Dhcr7L-KO mice, suggesting hepatic disruption of post-squalene cholesterol synthesis leads to minimal impact on sterol metabolism in the liver. This validated conditional Dhcr7 knockout model may now allow us to systematically explore the pathophysiology of SLOS, by allowing for temporal, cell and tissue-specific loss of DHCR7.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Kanuri B,Fong V,Ponny SR,Tallman KA,Ramachandra Rao S,Porter NA,Fliesler SJ,Patel SBdoi
10.1194/jlr.RA120001101subject
Has Abstractpub_date
2020-11-17 00:00:00eissn
0022-2275issn
1539-7262pii
jlr.RA120001101pub_type
杂志文章abstract：:The content of serum gangliosides was examined in VM and C57BL/6J (B6) mice that contained subcutaneous metastatic (VM) and non-metastatic (CT-2A) brain tumors, respectively. Gas-liquid chromatography (GLC) and high performance thin-layer chromatography (HPTLC) were used to analyze the serum gangliosides. N-glycolylne...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:The rate of peroxidation of unconjugated bilirubin (UCB), catalyzed by horseradish peroxidase (HRP), has been employed by Jacobsen (1969. FEBS Lett. 5: 112-114) to assess the fraction of unbound UCB in the presence of serum albumin. We used this method to examine the interactions of UCB with taurocholate (TC) at pH 8....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
abstract：:Percent cholesterol absorption was measured in 94 normal subjects aged 17- 80 years while consuming diets generally low in cholesterol (mean intake = 226 +/- 126 mg/day). A new dual stable isotope method was used where a cholesterol tracer containing 6 extra mass units was given intravenously and another tracer with 5...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:The objective of this study was to investigate the mobilization of individual fatty acids from human subcutaneous adipose tissue in vivo. Concentrations of individual non-esterified fatty acids were measured in arterialized plasma and in the venous drainage from subcutaneous abdominal adipose tissue in eight normal su...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:In mammals, vitamin A is primarily stored as retinyl esters in hepatic stellate cells under normal dietary intake of the vitamin. Previously, extrahepatic vitamin A-storing stellate cells have only been identified in animals maintained on a vitamin A-rich diet, and it has not been known whether these cells play a role...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
abstract：:Recent studies suggest that 7-dehydrocholesterol (7-DHC)-derived oxysterols play important roles in the pathophysiology of Smith-Lemli-Opitz syndrome (SLOS), a metabolic disorder that is caused by defective 3β-hydroxysterol-Δ(7)-reductase (DHCR7). Although 14 oxysterols have been identified as the primary products of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M035733
更新日期：2013-04-01 00:00:00
abstract：:The factors involved in shuttling cholesterol among cellular membranes have not been defined. Using amphotericin B selection, we previously isolated Chinese hamster ovary cell mutants expressing defects in intracellular cholesterol transport. Complementation analysis among seven mutants identified one cell line, mutan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:As microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apoB-containing lipoproteins by intestinal epithelial cells, the characterization and regulation of MTP in human intestinal cells, CaCo-2, was studied. CaCo-2 cells express MTP mRNA of 4.2 kb and a 97 kDa subunit of MTP pro...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:We propose a simple mathematical model to account for the coupling of secretion rates of bile salts, lecithin, and cholesterol into bile. The model assumes that: 1) molecules of "biliary" lecithin and cholesterol enter a functional compartment located in the endoplasmic reticulum of the hepatocyte from which they are ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Apolipoprotein (apo) A-I-containing lipoproteins can be separated into two subfractions, pre-beta HDL and alpha HDL (high density lipoproteins), based on differences in their electrophoretic mobility. In this report we present results indicating that these two subfractions are metabolically linked. When plasma was inc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-12-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M017822
更新日期：2012-01-01 00:00:00
abstract：:Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in choles...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M045294
更新日期：2014-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600297-JLR200
更新日期：2006-11-01 00:00:00
abstract：:Fungal lipases and human pancreatic lipase (hPL) share a common tertiary structure termed the alpha/beta hydrolase fold. In contrast, the region C-terminal to the common tertiary structure does not share any common structural features with fungal lipases, leading to the hypothesis that the divergent C-terminal domain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:Changes in the cellularity of various adipose tissues in growing cattle were analyzed. Fifty male cattle were slaughtered between 15 and 65% of mature weight. The whole adipose mass, separated by dissection, was divided into three parts: subcutaneous, intermuscular, and internal adipose tissues. Lipid content, cell si...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while se...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:The technique of short bed--continuous development chromatography has been utilized to increase the separation of glycosphingolipids on high performance thin-layer chromatography plates. The theoretical goal of increasing separation of bands by decreasing solvent strength was achieved within a practical time span as a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300091-JLR200
更新日期：2003-08-01 00:00:00
abstract：:Polymorphic transformations in two saturated-unsaturated mixed acid triacylglycerols, SOS (sn -1,3-distearoyl-2-oleoylglycerol) and OSO (sn -1,3-dioleoyl-2-stearoylglycerol), have been studied by FT-IR spectroscopy using deuterated specimens in which stearoyl chains are fully deuterated. A reversible phase transition ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:Biliary amphipathic anionic polypeptide (APF) the major protein of the pigment-lipoprotein complex in bile, and calcium-binding protein (CBP) from gallstones are both small (less than 10 kDa), highly acidic, amphipathic proteins present in bile and closely associated also with pigmented areas in human gallstones. Poly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-05-01 00:00:00
abstract：:Xanthophyllomyces dendrorhous is a basidiomycete yeast known as a natural producer of astaxanthin, a carotenoid of commercial interest because of its antioxidant properties. Recent studies indicated that X. dendrorhous has a functional SREBP pathway involved in the regulation of isoprenoid compound biosynthesis, which...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000431
更新日期：2020-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400377-JLR200
更新日期：2005-02-01 00:00:00
abstract：:De novo synthesis and turnover of endogenous ceramide in cultured skin fibroblasts from patients affected with Farber lipogranulomatosis were studied by biosynthetical labeling of cellular sphingolipids with [14C]serine. The cellular uptake of [14C]serine and incorporation into de novo synthesized ceramide was similar...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardiac events is still debated. In addition to its historically wel...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.S092007
更新日期：2019-04-01 00:00:00
abstract：:The biosynthesis of prostaglandins by isolated rat adrenocortical cells has been studied by determinations of products formed during incubations with labeled arachidonic acid and by radioimmunoassays. Analysis by thin-layer chromatographic separation of silicic acid column fractions indicated that PGE2, PGA2, (B2) and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：:The recognition that the 7 alpha-hydroxylation of 27-hydroxycholesterol is catalyzed by an enzyme that is different from cholesterol 7 alpha-hydroxylase raises the question as to the number of similar enzymes that may be present in liver and subserve bile acid synthesis. Thus, both 3 beta-hydroxy-5-cholestenoic acid a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The surface area, A, of contracting fatty acid monolayers was measured as a function of time, t, at constant surface pressure. In the initial temporal phase, ln A was linear with radical t. In a subsequent steady-state phase, ln A was linear with t. The initial desorption coefficient for sodium palmitate, K(i), and th...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-01-01 00:00:00
