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C Renard

Publications and source records attributed to C Renard.

At least 19 recordsLinked to original sources

The genomic sequence and analysis of the swine major histocompatibility complex.

We describe the generation and analysis of an integrated sequence map of a 2.4-Mb region of pig chromosome 7, comprising the classical class I region, the extended and classical class II regions, and the class III region of the major histocompatibility complex (MHC), also known as swine leukocyte antigen (SLA) complex. We have identified and manually annotated 151 loci, of which 121 are known genes (predicted to be functional), 18 are pseudogenes, 8 are novel CDS loci, 3 are novel transcripts, and 1 is a putative gene. Nearly all of these loci have homologues in other mammalian genomes but orthologues could be identified with confidence for only 123 genes. The 28 genes (including all the SLA class I genes) for which unambiguous orthology to genes within the human reference MHC could not be established are of particular interest with respect to porcine-specific MHC function and evolution. We have compared the porcine MHC to other mammalian MHC regions and identified the differences between them. In comparison to the human MHC, the main differences include the absence of HLA-A and other class I-like loci, the absence of HLA-DP-like loci, and the separation of the extended and classical class II regions from the rest of the MHC by insertion of the centromere. We show that the centromere insertion has occurred within a cluster of BTNL genes located at the boundary of the class II and III regions, which might have resulted in the loss of an orthologue to human C6orf10 from this region.

Animals↗

The persistent left superior vena cava: anatomical study, pathogenesis and clinical considerations.

The persistence of a left superior vena cava (LSVC) is an intrinsically cardiac anomaly, which can lead to serious complications during catheterization via the subclavian or internal jugular vein. We found this anomaly during dissection associated with an abnormal origin of the vertebral artery originating from the aortic arch between the left common carotid and subclavian arteries. The LSVC coursed towards the right atrium through a very dilated coronary sinus ostium. No abnormality of the azygos system was found. A thorough anatomic description was then made with external and internal morphology. The embryonic development and variations are described. Radiological and clinical implications are discussed.

Aged↗

Role of diabetes in atherosclerotic pathogenesis. What have we learned from animal models?

Diabetes mellitus is associated with a greater risk of developing atherosclerosis and its complications: stroke, myocardial infarction, and peripheral vascular disease. In patients with diabetes, atherosclerosis represents a complex multifactorial disease with increased lesion progression and severity compared to the nondiabetic population. Several risk factors have been proposed to explain the increased risk of cardiovascular disease with diabetes. They include: hyperglycaemia, dyslipidemia, accelerated formation of advanced glycation end-products (AGEs), increased oxidative stress, and genetic factors. It is difficult to precisely establish the elements leading to diabetes-accelerated atherosclerosis by means of epidemiological studies because all these factors coexist in diabetic patients. Thus, diabetic animal models that reproduce exacerbation of atherosclerosis would be helpful to understand why atherosclerosis is accelerated by diabetes, and to design appropriate treatments to limit its progression. This review analyzes most of the animal models developed to reproduce diabetes-accelerated atherosclerosis, and summarizes the effects of hyperglycaemia and lipid abnormalities on atherogenesis.

Animals↗

Nomenclature for factors of the SLA class-I system, 2004.

A systematic nomenclature for the genes and alleles of the swine major histocompatibility complex (MHC) is essential to the development and communication of research in swine immunology. The Swine Leucocyte Antigen (SLA) Nomenclature Committee of the International Society for Animal Genetics has reviewed all of the DNA sequence information for MHC class-I genes, available in GenBank/EMBL/DDBJ databases, and the associated published reports in order to develop such a systematic nomenclature. This report summarizes the proposed nomenclature, which parallels the World Health Organization's nomenclature for factors of the human MHC. The classical class-I SLA genes are designated as SLA-1, SLA-2 and SLA-3; the non-classical as SLA-6, SLA-7 and SLA-8. Nomenclature assignments for all SLA class-I GenBank sequences are now noted. The Committee will add new SLA class-I allele designations, as they are discovered, and will maintain a publicly available list of all recognized genes and alleles by using the International ImMunoGeneTics Project and its Immuno Polymorphism Database/MHC (IPD/MHC) sequence database for MHC sequences in veterinary species.

Alleles↗

Nomenclature for factors of the swine leukocyte antigen class II system, 2005.

A systematic nomenclature for the genes and alleles of the swine major histocompatibility complex (MHC) is essential to the development and communication of research in swine immunology. The Swine Leukocyte Antigen (SLA) Nomenclature Committee of the International Society for Animal Genetics (ISAG) has reviewed all of the DNA-sequence information for MHC class II genes, available in GenBank/EMBL/DDBJ databases, and the associated published reports to develop such a systematic nomenclature. This article summarizes the proposed nomenclature, which parallels the World Health Organization's nomenclature for factors of the human MHC. The SLA class II genes expressed on the cell membrane will be noted as SLA-DRA, SLA-DRB1, SLA-DQA, and SLA-DQB1. Nomenclature assignments for all SLA class II GenBank sequences are now noted. The committee will add new SLA class II allele designations, as they are discovered, and will maintain a publicly available list of all recognized genes and alleles using the Immuno Polymorphism Database (IPD). The sequences will be available from the IPD-MHC section of the database which contains non-human MHC sequences (http://www.ebi.ac.uk/ipd/mhc/sla/).

Animals↗

Detection of polymorphisms in the prion protein gene in the Belgian sheep population: some preliminary data.

The development of clinical signs of TSE/scrapie in sheep has been linked to polymorphisms in the prion protein (PRNP) gene. The most important polymorphisms appear to be at codons 136, 154, and 171. The objective of this study was to investigate the polymorphisms at these codons in the Belgian sheep population, including clinical healthy animals, healthy animals at the slaughterhouse and animals in TSE/scrapie positive farms (including a Nor98 farm).

Animals↗

Detection of quantitative trait loci for fat androstenone levels in pigs.

A QTL analysis of fat androstenone levels from a three-generation experimental cross between Large White and Meishan pig breeds was carried out. A total of 485 F2 males grouped in 24 full-sib families, their 29 parents and 12 grandparents were typed for 137 markers distributed over the entire porcine genome. The F2 male population was measured for fat androstenone levels at 100, 120, 140, and 160 d of age and at slaughter around 80 kg liveweight. Statistical analyses were performed using two interval mapping methods: a line-cross (LC) regression method, which assumes alternative alleles are fixed in founder lines, and a half- full-sib (HFS) maximum likelihood method, where allele substitution effects were estimated within each half- and full-sib family. Both methods revealed genomewide significant gene effects on chromosomes 3, 7, and 14. The QTL explained, respectively, 7 to 11%, 11 to 15%, and 6 to 8% of phenotypic variance. Three additional significant QTL explaining 4 to 7% of variance were detected on chromosomes 4 and 9 using LC method and on chromosome 6 using HFS method. Suggestive QTL were also obtained on chromosomes 2, 10, 11, 13, and 18. Meishan alleles were associated with higher androstenone levels, except on chromosomes 7, 10, and 13, although 10 and 13 additive effects were near zero. The QTL had essentially additive effects, except on chromosomes 4, 10, and 13. No evidence of linked QTL or imprinting effects on androstenone concentration could be found across the entire porcine genome. The steroid chromosome P450 21-hydroxylase (CYP21) and cytochrome P450 cholesterol side chain cleavage subfamily XIA (CYP11A) loci were investigated as possible candidate genes for the chromosome 7 QTL. No mutation of coding sequence has been found for CYP21. Involvement of a candidate regulatory mutation of CYP11A gene proposed by others can be excluded in our animals.

Adipose Tissue↗

Genetic linkage mapping of quantitative trait loci for behavioral and neuroendocrine stress response traits in pigs.

A QTL analysis of behavioral and neuroendocrine responses to a "novel environment" stress was conducted in a three-generation experimental cross between Meishan and Large White pig breeds. A total of 186 F2 males and 182 F2 females were studied for their behavioral and neuroendocrine reactivity to a novel environment test at 6 wk of age. Locomotion, vocalization, and defecation rate, as well as exploration time, were measured for 10 min. Blood samples were taken immediately before and after the test to measure plasma levels of ACTH, cortisol, and glucose. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using two interval mapping methods: a line-cross regression method, where founder lines were assumed to be fixed for different QTL alleles, and a half-/full-sib maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Both methods revealed a highly significant gene effect for poststress cortisol level (P < 0.001) and a significant effect for basal cortisol level (P < 0.05) at the end of the q arm of chromosome 7, explaining, respectively, 20% and 7% of the phenotypic variance. Meishan alleles are associated with higher cortisol levels and are partially dominant (for poststress levels) over Large White alleles. Other significant gene effects on biological measures were detected on chromosomes 1 and 17 (ACTH response to stress), 3, 5, and 8 (glucose levels). The SSC 17 QTL explains 12% of the phenotypic variance of poststress ACTH levels, with a suggestive evidence of imprinting effects. Meishan alleles are associated with lower poststress ACTH levels. Gene effects of low amplitude only were found for behavioral reactivity traits. Considering the effects of stress neuroendocrine systems on energy fluxes and protein deposition, and the importance of stress reactivity for meat quality and animal welfare, these results open new perspectives for pig selection.

Adrenocorticotropic Hormone↗

Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021.

Sinorhizobium meliloti is an alpha-proteobacterium that forms agronomically important N(2)-fixing root nodules in legumes. We report here the complete sequence of the largest constituent of its genome, a 62.7% GC-rich 3,654,135-bp circular chromosome. Annotation allowed assignment of a function to 59% of the 3,341 predicted protein-coding ORFs, the rest exhibiting partial, weak, or no similarity with any known sequence. Unexpectedly, the level of reiteration within this replicon is low, with only two genes duplicated with more than 90% nucleotide sequence identity, transposon elements accounting for 2.2% of the sequence, and a few hundred short repeated palindromic motifs (RIME1, RIME2, and C) widespread over the chromosome. Three regions with a significantly lower GC content are most likely of external origin. Detailed annotation revealed that this replicon contains all housekeeping genes except two essential genes that are located on pSymB. Amino acid/peptide transport and degradation and sugar metabolism appear as two major features of the S. meliloti chromosome. The presence in this replicon of a large number of nucleotide cyclases with a peculiar structure, as well as of genes homologous to virulence determinants of animal and plant pathogens, opens perspectives in the study of this bacterium both as a free-living soil microorganism and as a plant symbiont.

Bacterial Proteins↗

Antifibrotic action of Cu/Zn SOD is mediated by TGF-beta1 repression and phenotypic reversion of myofibroblasts.

Skin fibrosis is characterized by the proliferation and accumulation of activated fibroblasts called myofibroblasts. They exhibit specific cytoskeletal differentiation, overexpress the fibrogenic cytokine TGF-beta1, synthesize excess extracellular matrix compounds and exhibit a depleted antioxidant metabolism. Recently, SOD was successfully used as an antifibrotic agent in vivo, thus challenging the postulate of established fibrosis irreversibility. We postulated that myofibroblasts could be a direct target for this therapeutic effect. To test this hypothesis, we used three-dimensional co-culture models of skin, in which specific phenotypes of normal fibroblasts versus myofibroblasts are retained. These 3-D models were treated with liposomal and carrier-free Cu/Zn SOD, and examined for their effects on cell number, cell death, and phenotypic differentiation. The results show that SOD did not induce myofibroblast cell death, whereas it significantly reduced TGF-beta1 expression, thus demonstrating that SOD might be proposed as a potent antagonist of this major fibrogenic growth factor. We also found that SOD significantly lowered the levels of the myofibroblast marker alpha-sm actin, of beta-actin, and of the extracellular matrix components alpha1(I) collagen and tenascin-C. In conclusion, our results suggest that SOD antifibrotic action occurred in vitro through the reversion of myofibroblasts into normal fibroblasts.

Actins↗

Sequence of the pig major histocompatibility region containing the classical class I genes.

A segment comprising 307,078 nucleotides of the pig major histocompatibility complex (SLA) was completely sequenced. The segment corresponded to the entire SLA classical class I-containing region of the serologically defined SLA H01 haplotype. In all, 11 genes were characterized, comprising 7 class I genes located on the centromeric part of the sequence (SLA-1, 2, 3, 4, 5, 9, and 11) and 4 ring finger-related family genes located on its telomeric part. No member of one family was intermingled with a member of the other or with any third-party gene. All class I genes except SLA-11 were similarly orientated. The SLA-1, 2, and 3 genes displayed both promoter and overall coding regions compatible with normal functions. The SLA-4, 11, and 9 genes were considered pseudogenes because they exhibited marked anomalies. Although the SLA-5 gene had a complete coding region, it displayed mutations in promoter elements which could modify its expression. The great molecular similarity observed among the class I genes extended far outside them, and resulted from segmental duplications. The ring finger genes exhibited great homology with their human counterparts. In pig, one of these genes appeared to correspond to a complete gene which in humans is probably a pseudogene. In all, the 11 genes characterized span about 20% of the total sequence. The remaining 80% consists of interspersed repeat elements. The present results, together with the sequence previously reported involving the SLA class I-related genes, open the way for a better understanding of pig MHC organization.

Alleles↗

In the QTL region surrounding porcine MHC, gene order is conserved with human genome.

On the porcine genome, the region surrounding the Major Histocompatibility Complex, also called Swine Leukocyte Antigens (SLA), is of particular interest not only owing to itq role in the control of immune response, but also because of its influence on many traits such as growth, fatness, and meat quality. To help in the identification of responsible genes, detailed comparative maps of the MHC region in mammalian species and powerful mapping tools allowing accurate ordering of genes and markers in this region are needed. In this report, we describe the use of the recently developed IMpRH radiation hybrid panel, to construct a higher density radiation hybrid map of swine Sscr 7p-q12, containing 23 additional loci. Our results show that the gene order is conserved between the two MHC-containing regions, even if an inversion is observed above the QTL region in the region containing DEK, SCA1, and EDN1 genes. The framework map produced shows that the IMpRH panel permits the ordering of genes and markers in the three MHC classes and would thus allow accurate localization of ESTs and candidate genes.

Animals↗

Sequence of the swine major histocompatibility complex region containing all non-classical class I genes.

A segment of 158,063 nucleotides of the pig major histocompatibility complex (SLA) and corresponding to the junction of the class I and class III regions was sequenced entirely. The centromeric part of the segment contained six class III genes including the three tumor necrosis factor genes, while the telomeric part contained three genes belonging to the class I region. The order and the molecular organization of these genes were exactly conserved in the SLA and HLA complexes, except for the SC1 gene which displayed a shift of the reading frame in swine. The cluster of the three SLA class I-related genes (Ib) and the MIC1 and MIC2 genes were located in the middle of the segment, in the following order from the centromeric side onwards, SLA-6, SLA-7, SLA-8, MIC-1 and MIC-2. All three SLA Ib genes displayed an overall molecular structure compatible with the expression of membrane-anchored glycoproteins. The SLA-7 and SLA-8 genes bear greater resemblance than to the SLA-6 gene. Six SLA-6 alleles have been previously defined differing each from the other by unique point mutations. One of them, appeared to have arisen through the occurrence of a gene conversion event in which the SLA-7 gene served as template. Only MIC-2 gene might be functional, the second MIC-1 gene being truncated. In all, the 14 genes characterized spans 37% of the total sequence. The remaining 63% nucleotides comprised a number of repeat DNA motives, including LINE fragments, SINEs, microsatellites, and also numerous nucleotide stretches not yet defined in swine.

Alleles↗

Thymic T-cell tolerance of neuroendocrine functions: physiology and pathophysiology.

Intimate interactions between the two major systems of cell-to-cell communication, the neuroendocrine and immune systems, play a pivotal role in homeostasis and developmental biology. During phylogeny as well as during ontogeny, the molecular foundations of the neuroendocrine system emerge before the generation of diversity within the system of immune defenses. Before reacting against non-self infectious agents, the immune system has to be educated in order to tolerate the host molecular structure (self). The induction of self-tolerance is a multistep process that begins in the thymus during fetal ontogeny (central tolerance) and also involves anergizing mechanisms outside the thymus (peripheral tolerance). The thymus is the primary lymphoid organ implicated in the development of competent and self-tolerant T-cells. During ontogeny, T-cell progenitors originating from hemopoietic tissues (yolk sac, fetal liver, then bone marrow) enter the thymus and undergo a program of proliferation, T-cell receptor (TCR) gene rearrangement, maturation and selection. Intrathymic T-cell maturation proceeds through discrete stages that can be traced by analysis of their cluster differentiation (CD) surface antigens. It is well established that close interactions between thymocytes (pre-T-cells) and the thymic cellular environment are crucial both for T-cell development and for induction of central self-tolerance. Particular interest has focused on the ability of thymic stromal cells to synthesize polypeptides belonging to various neuroendocrine families. The thymic repertoire of neuroendocrine-related precursors recapitulates at the molecular level the dual role of the thymus in T-cell negative and positive selection. Thymic precursors not only constitute a source of growth factors for cryptocrine signaling between thymic stromal cells and pre-T-cells, but are also processed in a way that leads to the presentation of self-antigens by (or in association with) thymic major histocompatibility complex (MHC) proteins. Thymic neuroendocrine self-antigens usually correspond to peptide sequences highly conserved during the evolution of their corresponding family. The thymic presentation of some neuroendocrine self-antigens does not seem to be restricted by MHC alleles. Through the presentation of neuroendocrine self-antigens by thymic MHC proteins, the T-cell system might be educated to tolerate main hormone families. More and more recent experiments support the concept that a defect in thymic tolerogenic function is implicated as an important factor in the pathophysiology of autoimmunity.

Animals↗

Thymic neuroendocrine self-antigens. Role in T-cell development and central T-cell self-tolerance.

The repertoire of thymic neuroendocrine precursors plays a dual role in T-cell differentiation as the source of either cryptocrine accessory signals in T-cell development or neuroendocrine self-antigens presented by the thymic major histocompatibility complex (MHC) machinery. Thymic neuroendocrine self-antigens usually correspond to peptide sequences highly conserved during the evolution of one family. The thymic presentation of some neuroendocrine self-antigens is not restricted by MHC alleles. Oxytocin (OT) is the dominant peptide of the neurohypophysial family. It is expressed by thymic epithelial and nurse cells (TEC/TNCs) of different species. Ontogenetic studies have shown that the thymic expression of the OT gene precedes the hypothalamic one. Both OT and VP stimulate the phosphorylation of p125FAK and other focal adhesion-related proteins in murine immature T cells. These early cell activation events could play a role in the promotion of close interactions between thymic stromal cells and developing T cells. It is established that such interactions are fundamental for the progression of thymic T-cell differentiation. Insulin-like growth factor 2 (IGF-2) is the dominant thymic polypeptide of the insulin family. Using fetal thymic organ cultures (FTOCs), the inhibition of thymic IGF-2-mediated signaling was shown to block the early stages of T-cell differentiation. The treatment of FTOCs with an mAb anti-(pro)insulin had no effect on T-cell development. In an animal model of autoimmune type 1 diabetes (BB rat), thymic levels of (pro)insulin and IGF-1 mRNAs were normal both in diabetes-resistant and diabetes-prone BB rats. IGF-2 transcripts were clearly identified in all thymuses from diabetes-resistant adult (5-week) and young (2- and 5-days) BB rats. In marked contrast, the IGF-2 transcripts were absent and the IGF-2 protein was almost undetectable in +/- 80% of the thymuses from diabetes-prone adult and young BB rats. These data show that a defect of the thymic IGF-2-mediated tolerogenic function might play an important role in the pathophysiology of autoimmune Type 1 diabetes.

Adult↗

Involvement of insulin-like growth factors in early T cell development: a study using fetal thymic organ cultures.

The expression of insulin-like growth factor (IGF) and IGF receptor genes was investigated by RT-PCR during ontogeny of the murine thymus. IGF-1, IGF-1R, M6P/IGF-2R genes are expressed in the thymus both in fetal and postnatal life, whereas IGF-2 messenger RNAs (mRNAs) decline after birth but are still detectable on the seventh week. By in situ hybridization, IGF-2 transcripts were located in the outer cortex and medulla of the postnatal thymus, and on the whole surface ofthe epithelial-like network in the fetal thymus. The effects of anti-IGFs and IGF-receptors neutralizing Abs on the generation of pre-T cell subpopulations were then investigated using fetal thymic organ cultures (FTOC). FTOC treatment with an anti-IGF-2 mAb, an anti-IGF-1R mAb, or an anti-M6P/IGF-2R polyclonal Ab induced a blockade of T cell differentiation at the CD4-CD8- stage, as shown by a significant increase in the percentage of CD4-CD8- cells and a decrease in the percentage of CD4+CD8+ cells. Moreover, anti-IGF-2 Ab treatment induced an increase in CD8+ cells suggesting that thymic IGF-2 might have a role in determining differentiation into the CD4 or CD8 lineage. Anti-IGF-1 Ab treatment decreased the proportion in CD4-CD8- cells and increased the frequency in CD4+CD8+. FTOC treatment with anti-(pro)insulin did not exert any significant effect on T cell development. These data indicate that the intrathymic IGF-mediated signaling plays an active role in the early steps of T cell differentiation during fetal development.

Animals↗

Time- and dose-dependent digoxin redistribution by digoxin-specific antigen binding fragments in a rat model.

To study the influence of the interval between digoxin intake and digoxin-specific antigen binding fragment (DSFab) administration, we developed a rat kinetic model. 3H-digoxin (0.77 nmol/kg) was injected by intravenous route and DSFab was injected at different times (12, 30 or 60 min) corresponding to different levels of 3H-digoxin distribution (50, 83 and 100%). The effect of increasing the molar DSFab/3H-digoxin ratio from 1 to 5 was also investigated. To evaluate DSFab effect on the 3H-digoxin pharmacokinetics, we also investigated the pharmacokinetics of the 125I-DSFab and DSFab-3H-digoxin complex. 3H-digoxin and DSFab-3H-digoxin complex pharmacokinetics showed that DSFab altered immunoreactive 3H-digoxin pharmacokinetics. In redistribution studies performed 12, 30 or 60 min after 3H-digoxin injection, DSFab bound immunoreactive 3H-digoxin including native 3H-digoxin and active metabolites of 3H-digoxin. This binding induced a redistribution process of immunoreactive 3H-digoxin in the DSFab distribution compartment and was evaluated by the redistribution fraction (F(R)). F(R) was 23% lower at 60 min than at 12 and 30 min, and by increasing the DSFab/3H-digoxin ratio from 1 to 5, F(R) increased by 60%. In conclusion, the longer the time interval between digoxin intake and DSFab administration, the lower the efficacy of the redistribution process. This effect could be reduced by increasing the DSFab dose.

Animals↗

Spatial arrangement of pig MHC class I sequences.

Bacterial artificial chromosome (BAC) clones were assigned within the pig major histocompatibility complex (Mhc) by polymerase chain reaction-screening and Southern blot hybridization using sequence-tagged site (STS) markers and BAC end-rescued sequences. In all, 35 BAC clones were discovered containing 12 anchor genes of the SLA class I region and two genes of the SLA class III region. Twenty of these 35 clones comprised two distinct class I gene clusters, each spanning about 100 kilobases. One cluster enclosed three class I related genes (SLA-6 to -8) and two genes (MIC-1 and MIC-2) more distantly related to class I. The other cluster enclosed typical class I genes, of which three (SLA-1, -2, and -3) were transcribed by fibroblasts homozygous for the H01 haplotype which we used to construct a pig BAC library. Ordered clones are certainly helpful in isolating agronomically, biologically, and medically important genes. They would also be useful for inducing genetic modifications in pig cell lines.

Animals↗