ABSTRACT
Diarrhoea, a significant problem in pig rearing industry affecting pre- and post-weaning piglets is caused by enterotoxigenic Escherichia coli (ETEC). The ETEC are classified as per the fimbriae types which are responsible for bacterial attachment with enterocytes and release of toxins causing diarrhoea. However, genetic difference exists for susceptibility to ETEC infection in piglets. The different phenotypes found in pigs determine their (pigs') susceptibility or resistance towards fimbrial subtypes/variants (F4ab, F4ac, F4ad and F18). Specific receptors are present on intestinal epithelium for attachment of these fimbriae, which do not express to same level in all animals. This differential expression is genetically determined and thus their genetic causes (may be putative candidate gene or mutations) render some animals resistant or susceptible to one or more fimbrial subtypes. Genetic linkage studies have revealed the mapping location of the receptor loci for the two most frequent variants F4ab and F4ac to SSC13q41 (i.e. q arm of 13th chromosome of Sus scrofa). Some SNPs have been identified in mucin gene family, transferring receptor gene, fucosyltransferase 1 gene and swine leucocyte antigen locus that are proposed to be linked mutations for resistance/susceptibility towards ETEC diarrhoea. However, owing to the variety of fimbrial types and subtypes, it would be difficult to identify a single causative mutation and the candidate loci may involve more number of genes/regions. In this review, we focus on the genetic mutations in genes involved in imparting resistance/susceptibility to F4 or F18 ETEC diarrhoea and possibilities to use them as marker for selection against susceptible animals.
Subject(s)
Enterotoxigenic Escherichia coli , Escherichia coli Infections/veterinary , Genetic Predisposition to Disease , Swine Diseases/microbiology , Animals , Diarrhea/genetics , Diarrhea/microbiology , Diarrhea/veterinary , Escherichia coli Infections/genetics , Escherichia coli Infections/microbiology , Genetic Linkage , Polymorphism, Single Nucleotide , Swine , Swine Diseases/geneticsABSTRACT
The humoral barrier has been the limiting factor in moving xenotransplantation towards the clinic. Improvements in somatic cell nuclear transfer and genome editing, particularly CRISPR-Cas9, have made it possible to create pigs with multiple glycan xenoantigen deletions for the purposes of reducing xenoreactive antibody binding to the xenografted organ. Recent studies have also considered the aetiology and existence of antibodies directed at the swine leucocyte antigen (SLA) complex, and potential genetic engineering strategies to avoid these antibodies. Evaluation of xenoreactive antibody binding is very important for the advancement of xenotransplantation, because if patients do not have any detectable xenoreactive antibody, then it is reasonable to expect that cellular rejection and not antibody-mediated rejection (AMR) will be the next hurdle to clinical application.
Subject(s)
Antigens, Heterophile/immunology , Galactosyltransferases/immunology , Gene Knockout Techniques , Graft Rejection/prevention & control , Mixed Function Oxygenases/immunology , N-Acetylgalactosaminyltransferases/immunology , Swine/immunology , Transplantation, Heterologous , Animals , Animals, Genetically Modified/immunology , Antibodies, Heterophile/biosynthesis , Antibodies, Heterophile/immunology , Antigen-Antibody Reactions , Antigens, Heterophile/genetics , Epitopes/immunology , Galactosyltransferases/deficiency , Galactosyltransferases/genetics , Genetic Engineering , Graft Rejection/immunology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Humans , Mixed Function Oxygenases/deficiency , Mixed Function Oxygenases/genetics , N-Acetylgalactosaminyltransferases/deficiency , N-Acetylgalactosaminyltransferases/genetics , Transplantation ImmunologyABSTRACT
We have characterized swine leucocyte antigen (SLA) classes I and II molecules of a domestic pig as a model for use in our xenotransplant program. Molecular characterization of the SLA classes I and II genes is critical to understanding the adaptive immune responses between swine and humans in the event of xenotransplantation. Seven swine leucocyte antigen genes (SLA-1, SLA-2, SLA-3, DQB1, DRB1, DQA and DRA) were analyzed and 15 alleles were identified. A novel DRA*w04re01 is reported for this limited polymorphic class II gene. The heterozygous haplotypes, Hp-32.0/35.0 and Hp-0.13/0.23 were deduced for our IU-pig model, for SLA classes I and II regions, respectively.