Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs

Jacobsen, Mette Juul; Cirera, Susanna; Joller, David; Esteso, Gloria; Kracht, Steffen S; Edfors, Inger; Berthou, Christian; Archibald, Alan; Vögeli, P.; Neuenschwander, Stefan; Bertschinger, H. U.; Rampoldi, Antonio; Andersson, Leif; Fredholm, Merete; Jørgensen, Claus B.

doi:10.1186/1756-0500-4-225

Cited by 23 publications

(34 citation statements)

References 23 publications

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“…In addition to MUC13 , two other genes, encoding structurally similar cell surface mucins and also located on Chr13, are known to be expressed in porcine jejunum: MUC4 and MUC20 [3]. To identify whether there is interaction between MUC13 or ITGB5 with each of the two mucin genes, we firstly separately compared the mRNA expression levels of MUC4 and MUC20 in ITGB5 - or MUC13 -deficient cells with that in the negative control cells at 44 h post-transfection of siRNAs.…”

Section: Resultsmentioning

confidence: 99%

“…As both ITGB5 and MUC13 are candidate genes for ETEC F4ac receptor [3], [11], we finally assessed the influences of these two genes on adhesion of F4ac ETEC to the piglet small intestinal epithelial cells (Figure 4). IPEC-J2 cells were separately transfected with ITGB5 - or MUC13 -targeting siRNA for 48 h, and the cells were co-cultured with live bacteria for a further 3 h. Quantitative real-time PCR was used to measure the counts of adherent bacteria as described previously [5].…”

Section: Resultsmentioning

confidence: 99%

“…F4 fimbriae are the major colonization factors associated with porcine neonatal and postweaning diarrhoea caused by ETEC [2], [3]. Among the three different antigenic variants (F4ab, F4ac, and F4ad) of F4 fimbriae, F4ac is the most prevalent [4], [5].…”

Section: Introductionmentioning

confidence: 99%

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Gene Silencing of Porcine MUC13 and ITGB5: Candidate Genes towards Escherichia coli F4ac Adhesion

Zhou

Liu

et al. 2013

PLoS ONE

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BackgroundIntegrin beta-5 (ITGB5) and mucin 13 (MUC13) genes are highly expressed on the apical surface of intestinal epithelia and are thought to be candidate genes for controlling the expression of the receptor for enterotoxigenic Escherichia coli (ETEC) F4ac. Human MUC13 protein has an expected role in protecting intestinal mucosal surfaces and porcine ITGB5 is a newly identified potential receptor for ETEC F4ac.Methodology/Principal FindingsTo test the hypothesis that ITGB5 and MUC13 both play key roles in protection of the intestinal mucosa against pathogenic bacterium, porcine intestinal epithelial cells (IPEC-J2) were transfected with ITGB5-targeting, MUC13-targeting or negative control small interfering RNA (siRNA), respectively. Firstly, we measured mRNA expression levels of mucin genes (MUC4, MUC20), pro-inflammatory genes (IL8, IL1A, IL6, CXCL2), anti-inflammatory mediator SLPI, and PLAU after RNAi treatments with and without ETEC infection. Secondly, we compared the adhesions of ETEC to the pre- and post-knockdown IPEC-J2 cells of ITGB5 and MUC13, respectively. We found that ITGB5 and MUC13 knockdown both had small but significant effects in attenuating the inflammation induced by ETEC infection, and both increased bacterial adhesion in response to F4ac ETEC exposure.Conclusions/SignificanceOur current study first reported that ITGB5 and MUC13 are important adhesion molecules of mucosal epithelial signaling in response to Escherichia coli in pigs. These data suggest that both ITGB5 and MUC13 play key roles in defending the attachment and adhesion of ETEC to porcine jejunal cells and in maintaining epithelial barrier and immunity function.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Gene Silencing of Porcine MUC13 and ITGB5: Candidate Genes towards Escherichia coli F4ac Adhesion

Zhou

Liu

et al. 2013

PLoS ONE

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“…S.typhimurium -infected pigs show reduced MUC4 expression on the surface of colonic epithelium compared with non-infected pigs, indicated that MUC4 is important in inflammatory response in colonic tissues [12]. Previously, we and other investigators reported MUC4 polymorphisms that were strongly associated with susceptibility to enterotoxigenic Escherichia coli (ETEC) F4ab/ac in pigs [13,14], although we recently demonstrated that susceptibility towards ETEC F4ac is governed by the MUC13 gene proximal to MUC4 (unpublished data). More recently, a variant in MUC4 has been evidenced to be significantly associated with prolificacy traits; MUC4 expression levels in the uterine of high prolific sows are two-fold greater than those in low prolific sows [15].…”

Section: Introductionmentioning

confidence: 99%

Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

Yang

Yan

et al. 2012

BMC Genet

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BackgroundMUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD) within this gene in Chinese indigenous breeds and Western commercial breeds.ResultsA total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb) in Western commercial breeds. The significant positive Tajima’D, and Fu and Li’s D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process.ConclusionsChinese and Western breeds have similar nucleotide diversity but evolve divergently in the MUC4 region. Western breeds exhibited unusual low LD extent at the MUC4 locus, reflecting the complexity of nucleotide variability of pig genome. The finding suggests that high density (e.g. 1SNP/10 kb) markers are required to capture the underlying causal variants at such regions.

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“…that the polymorphisms are not the causative mutations, but are good markers, and more accurate markers for F4acR than for F4abR [31]. Jacobsen et al also found one MUC20 -g.2387C>T SNP that perfectly matched the F4ab/acR phenotype in four tested animals, two resistant Wild Boars and two homozygous susceptible Large White [32]. However, genotyping of 42 additional animals of different breeds showed that this SNP is not associated with the phenotype of ETEC-F4ab/ac susceptibility [32].…”

Section: Genetic Research On F4 Receptors – the Positional Candidamentioning

confidence: 99%

The search for the gene mutations underlying enterotoxigenic Escherichia coli F4ab/ac susceptibility in pigs: a review

Schroyen

Stinckens

Verhelst

et al. 2012

Vet Res

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Diarrhoea due to enterotoxigenic Escherichia coli with fimbriae F4 (ETEC-F4) is an important problem in neonatal and just weaned piglets and hence for the pig farming industry. There is substantial evidence for a genetic basis for susceptibility to ETEC-F4 since not all piglets suffer from diarrhoea after an ETEC-F4 infection. It is assumed that the wild boar was originally ETEC-F4 resistant and that susceptibility towards ETEC arose after domestication. There are different phenotypes in the pig determined by which of the three existing F4 variants (F4ab, F4ac or F4ad) they are susceptible or resistant for. This suggests that several F4 receptors exist, expressed individually or in combination with each other on the brush border of the piglet’s small intestine. As such, the mucin-type glycoproteins (IMTGP) are described as F4ab/ac receptors, while the intestinal neutral glycospingolipid (IGLad) is proposed as an F4ad receptor. GP74 is a putative F4ab receptor. However, the specific genes that encode for the susceptibility are not yet known. In the past decades, linkage analyses revealed that the loci encoding for the receptor(s) for the two most frequent variants F4ab and F4ac were mapped to the 13th chromosome of the pig (Sus scrofa 13, SSC13). After fine mapping, the region of interest was mapped between two microsatellite markers, Sw207 and S0075, and interesting candidate genes surfaced. Numerous SNP analyses and a few expression studies on the three MUC-genes (MUC4, MUC13 and MUC20) and the transferrin receptor gene (TFRC) as well as on some other positional candidate genes have been performed in order to find the causative mutation for the ETEC-F4ab/ac receptor(s). However, until today, the exact mutation causing susceptibility to ETEC-F4 remains unknown.

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Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs

Cited by 23 publications

References 23 publications

Gene Silencing of Porcine MUC13 and ITGB5: Candidate Genes towards Escherichia coli F4ac Adhesion

Gene Silencing of Porcine MUC13 and ITGB5: Candidate Genes towards Escherichia coli F4ac Adhesion

Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

The search for the gene mutations underlying enterotoxigenic Escherichia coli F4ab/ac susceptibility in pigs: a review

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