Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S versus R rats

<p>Abstract</p> <p>Background</p> <p>To test whether epithelial sodium channel (ENaC) genes' variants contribute to salt sensitive hypertension in Dahl rats, we screened ENaC α, β, and γ genes entire coding regions, intron-exon junctions, and the 3' and 5' flanking regions in Dahl S, R and Wistar rats using both Denaturing High Performance Liquid Chromatography (DHPLC) and sequencing.</p> <p>Results</p> <p>Our analysis revealed no sequence variability in the three genes encoding ENaC in Dahl S <it>versus </it>R rats. One homozygous sequence variation predicted to result in a D75E substitution was identified in Dahl and Wistar rat ENaC α compared to Brown Norway. Six and two previously reported polymorphic sites in Brown Norway sequences were lost in Dahl and Wistar rats, respectively. In the 5' flanking regions, we found a deletion of 5GCTs in Dahl and Wistar rat ENaC α gene, five new polymorphic sites in ENaC β and γ genes, one homozygous sequence variation in Dahl and Wistar rat ENaC γ gene, as well as one Dahl rat specific homozygous insertion of -1118CCCCCA in ENaC γ gene. This insertion created additional binding sites for Sp1 and Oct-1. Five and three Brown Norway polymorphic sites were lost in Dahl and Wistar rats, respectively. No sequence variability in ENaC 3' flanking regions was identified in Dahl compared to Brown Norway rats.</p> <p>Conclusion</p> <p>The first comprehensive sequence analysis of ENaC genes did not reveal any differences between Dahl S and R rats that were isogenic in the regions screened. Mutations in ENaC genes intronic sequence or in ENaC-regulatory genes might possibly account for increased ENaC activity in Dahl S <it>versus </it>R rats.</p

Lamin A/C mutations in dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplant. Mutations in 60 genes have been associated with DCM. Approximately 6% of all DCM cases are caused by mutations in the lamin A/C gene (LMNA). LMNA codes for type-V intermediate filaments that support the structure of the nuclear membrane and are involved in chromatin structure and gene expression. Most LMNA mutations result in striated muscle diseases while the rest affects the adipose tissue, peripheral nervous system, multiple tissues or lead to progeroid syndromes/overlapping syndromes. Patients with LMNA mutations exhibit a variety of cellular and physiological phenotypes. This paper explores the current phenotypes observed in LMNA-caused DCM, the results and implications of the cellular and animal models of DCM and the prevailing theories on the pathogenesis of laminopathies.

Effects of Exercise Training on Molecular Markers of Lipogenesis and Lipid Partitioning in Fructose-Induced Liver Fat Accumulation

The present study was designed to investigate the impact of exercise training on lipogenic gene expression in liver and lipid partitioning following the ingestion of a high fructose load. Female rats were exercise-trained for 8 wk or kept sedentary before being submitted to a fasting/refeeding protocol. Rats were further subdivided as follow: rats were fasted for 24 h, refed a standard diet for 24 h, starved for another 24 h, and refed with a standard or a high-fructose diet 24 h before sacrifice. Fructose refeeding was associated with an increase in hepatic lipid content, endocannabinoid receptor 1, sterol regulatory element-binding protein1c, and stearoyl-CoA desaturase1 gene expression in both Sed and TR rats. However, desaturation indexes measured in liver (C16 : 1/C16 : 0 and C18 : 1/C18 : 0) and plasma (C18 : 1/C18 : 0) were higher (P < 0.01) in TR than in Sed rats following fructose refeeding. It is concluded that exercise training does not significantly affect fat accumulation and the molecular expression of genes involved in lipogenesis after fasting and fructose refeeding but does modify the partitioning of lipids so as to provide more unsaturated fatty acids in liver without affecting liver fat content

Cellular and Animal Models of Striated Muscle Laminopathies

The lamin A/C (LMNA) gene codes for nuclear intermediate filaments constitutive of the nuclear lamina. LMNA has 12 exons and alternative splicing of exon 10 results in two major isoforms&#8212;lamins A and C. Mutations found throughout the LMNA gene cause a group of diseases collectively known as laminopathies, of which the type, diversity, penetrance and severity of phenotypes can vary from one individual to the other, even between individuals carrying the same mutation. The majority of the laminopathies affect cardiac and/or skeletal muscles. The underlying molecular mechanisms contributing to such tissue-specific phenotypes caused by mutations in a ubiquitously expressed gene are not yet well elucidated. This review will explore the different phenotypes observed in established models of striated muscle laminopathies and their respective contributions to advancing our understanding of cardiac and skeletal muscle-related laminopathies. Potential future directions for developing effective treatments for patients with lamin A/C mutation-associated cardiac and/or skeletal muscle conditions will be discussed

Location of the variants identified in the 5' flanking region of Dahl S, R, and Wistar rats ENaC β gene on the Brown Norway rat genomic sequence 15

<p><b>Copyright information:</b></p><p>Taken from "Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S R rats"</p><p>http://www.biomedcentral.com/1471-2156/8/35</p><p>BMC Genetics 2007;8():35-35.</p><p>Published online 25 Jun 2007</p><p>PMCID:PMC1933436.</p><p></p> Position of the variants identified in the current study is highlighted in bold. Boxes represent the putative transcription factor-binding sequences; the putative binding sequences found during the present sequence analysis are labeled in bold; the factor names are written above the boxes. The first three bases for the major kidney and brain transcription start sites are italicized and bold. TFSEARCHscore for the newly assigned putative binding sequence for STATX is 92.3

Location of the variants identified in the 5' flanking region of Dahl S, R, and Wistar rats ENaC α gene on the Brown Norway rat genomic sequence 15

<p><b>Copyright information:</b></p><p>Taken from "Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S R rats"</p><p>http://www.biomedcentral.com/1471-2156/8/35</p><p>BMC Genetics 2007;8():35-35.</p><p>Published online 25 Jun 2007</p><p>PMCID:PMC1933436.</p><p></p> Position of the variants identified in the current study is highlighted in bold. Boxes represent the putative transcription factor-binding sequences; the putative binding sequences found during the present sequence analysis are labeled in bold; the factor names are written above the boxes. The first three bases for the major kidney and brain transcription start sites are italicized and bold. The translation initiation codon (+1) is underlined. TFSEARCHscores for the newly assigned putative binding sequences are 93.1, 89.7, and 89.7 for GATA 1, 2, 3 respectively; 89.0 and 88.5 for GATA 1, 2 respectively and 85.8 for YY1; 88.5 for GATA 2, and 87.7 for Sp1

Location of the variants identified in the 5' flanking region of Dahl S, R, and Wistar rats ENaC γ gene on the Brown Norway rat genomic sequence 15

<p><b>Copyright information:</b></p><p>Taken from "Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S R rats"</p><p>http://www.biomedcentral.com/1471-2156/8/35</p><p>BMC Genetics 2007;8():35-35.</p><p>Published online 25 Jun 2007</p><p>PMCID:PMC1933436.</p><p></p> Position of the variants identified in the current study is highlighted in bold. Boxes represent the putative transcription factor-binding sequences; the putative binding sequences found during the present sequence analysis are labeled in bold; the factor names are written above the boxes. The first three bases for the major kidney and brain transcription start sites are italicized and bold. The translation initiation codon (+1) is underlined. TFSEARCHscores for the newly assigned putative binding sequences are 89.2, 87.4, and 89.0 for C/EBP a & b and CRE, respectively; 85.8 for Oct-1; 89.3 for C/EBP, 87.9 and 85.5 for CRE and C/EBPb respectively; 87.7 for Sp1, 91.0 and 87.4 for c-Myc and C/EBPb respectively; and 85.9 for USF

Control of Biological Hazards in Insect Processing: Application of HACCP Method for Yellow Mealworm (Tenebrio molitor) Powders

Entomophagy has been part of human diets for a long time in a significant part of the world, but insects are considered to be a novel food everywhere else. It would appear to be a strategic alternative in the future of human diet to face the challenge of ensuring food security for a growing world population, using more environmentally sustainable production systems than those required for the rearing of other animals. Tenebrio molitor, called yellow mealworm, is one of the most interesting insect species in view of mass rearing, and can be processed into a powder that ensures a long shelf life for its use in many potential products. When considering insects as food or feed, it is necessary to guarantee their safety. Therefore, manufacturers must implement a Hazard Analysis Critical Control plan (HACCP), to limit risks for consumers&rsquo; health. The aim of this case study was to develop a HACCP plan for Tenebrio molitor larvae powders for food in a risk-based approach to support their implementation in industry. Specific purposes were to identify related significant biological hazards and to assess the efficiency of different manufacturing process steps when used as Critical Control Points. Then, combinations of four different processes with four potential uses of powders by consumers in burger, protein shake, baby porridge, and biscuits were analyzed with regard to their safety

Lamin A/C mutants disturb sumo1 localization and sumoylation in vitro and in vivo.

A-type lamins A and C are nuclear intermediate filament proteins in which mutations have been implicated in multiple disease phenotypes commonly known as laminopathies. A few studies have implicated sumoylation in the regulation of A-type lamins. Sumoylation is a post-translational protein modification that regulates a wide range of cellular processes through the attachment of small ubiquitin-related modifier (sumo) to various substrates. Here we showed that laminopathy mutants result in the mislocalization of sumo1 both in vitro (C2C12 cells overexpressing mutant lamins A and C) and in vivo (primary myoblasts and myopathic muscle tissue from the Lmna(H222P/H222P) mouse model). In C2C12 cells, we showed that the trapping of sumo1 in p.Asp192Gly, p.Gln353Lys, and p.Arg386Lys aggregates of lamin A/C correlated with an increased steady-state level of sumoylation. However, lamin A and C did not appear to be modified by sumo1. Our results suggest that mutant lamin A/C alters the dynamics of sumo1 and thus misregulation of sumoylation may be contributing to disease progression in laminopathies