Dataset Information

Comparative analysis of immune related genes between domestic pig and germ-free minipig.

ABSTRACT: Recently, minipig has been considered as an animal model that is appropriate for human disease model to study toxicology, pharmacology, and xenotransplantation. Nevertheless, minipigs are bred in various environment according to their use. Here, we suggest that minipigs used for research should be bred in well-controlled facility, comparing immune status of pigs raised in different breeding environment. DNA microarray was performed with ear skin and placenta of Landrace domestic pigs (DPs) and Minnesota germ-free minipigs (GPs). Their immune transcriptome was analyzed by gene ontology (GO) annotation database, based on criteria of |log₂ fold change| ?1 with P???0.05. As a result, we found that immune related genes in the ear skin of DPs were highly activated, compared to GPs. On the other hand, no significant s were found in the placenta. Quantitative real-time PCR (qRT-PCR) was performed in five candidate immune genes. Their fold changes were consistent with the results from DNA microarray (P???0.05). In conclusion, we experimentally proved that porcine immune system was affected by different breeding environment, suggesting the importance of controlling microbes in animal room for the qualified research.

SUBMITTER: Lee JY

PROVIDER: S-EPMC7709342 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Comparative analysis of immune related genes between domestic pig and germ-free minipig.

Lee Ju Young JY Kim Sang Eun SE Lee Hoon Taek HT Hwang Jeong Ho JH

Laboratory animal research 20201201 1

Recently, minipig has been considered as an animal model that is appropriate for human disease model to study toxicology, pharmacology, and xenotransplantation. Nevertheless, minipigs are bred in various environment according to their use. Here, we suggest that minipigs used for research should be bred in well-controlled facility, comparing immune status of pigs raised in different breeding environment. DNA microarray was performed with ear skin and placenta of Landrace domestic pigs (DPs) and M ...[more]

PMID: 33292811

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Project description:BackgroundIn recent years, significant progress has been made in immune checkpoint inhibitors (ICIs). However, accompanied by remarkable efficacy, a growing number of immune-related adverse events (irAEs) also arose. The mechanism of irAEs remains unclear. Previous studies indicated a positive association between specific human leukocyte antigen (HLA) variants and irAEs. Therefore, we planned and initiated a large cohort study aiming to uncover the relationship between irAEs and divergent HLA types.MethodsWe screened all patients who have been treated in the clinical research ward, Cancer Hospital of the Chinese Academy of Medical Sciences. All participants were diagnosed with malignant tumors with complete AE follow-up data in the original electronic medical records. Sequencing libraries were generated using a customized panel, and four-digit formatted HLA alleles were extracted for further analysis. Association analysis was performed between HLA variants and different irAEs. We introduced two external reference groups and a non-irAE control group within the study cohort to control the type I error. We also explored the relationship between the zygosity of HLA genes, the evolutionary divergence of HLA class I genotype (HED), and irAEs.Results530 participants received at least two doses of ICIs. The median follow-up time was 10.3 months. 97% of patients received anti-PD-1/PD-L1 treatment. The occurrence of overall irAEs showed no significant difference between the HLA homozygous group and the HLA heterozygous group. We did not find any significant association between irAEs and HED. We found that some HLA types are associated with irAEs of different organs and detected a significant association between HLA-DRB3*01:01 and thrombocytopenia (OR 3.48 (1.19,9.42), p = 0.011), HLA-DPB1*04:02 and hypokalemia/hyponatremia (OR 3.44 (1.24,9.1), p = 0.009), leukopenia (OR 2.1 (0.92,4.8), p = 0.037), anemia (OR 2.33 (1.0,5.41), p = 0.026), HLA-A*26:01 and bilirubin elevation (OR 2.67 (0.92,8.31), p = 0.037).ConclusionsIrAEs in specific organs and tissues may be associated with certain HLA types, while HLA heterogeneity has no significant influence on the happening of irAEs. More research is needed to explore the role of germline genetic changes in the risk assessment of irAEs.

Project description:The liver is a complex organ governing several physiological processes that define biological mechanisms affecting growth, feed efficiency and performance traits in all livestock species, including pig. Proteomics may contribute to a better understanding of the relationship between liver functions and complex production traits in pigs and to characterize this species as biomedical model. This study applied, for the first time, a label-free liquid chromatography-mass spectrometry (LC-MS) proteomic approach to compare the liver proteome profiles of two important heavy pig breeds, Italian Duroc and Italian Large White. Liver specimens were collected (after slaughtering) from performance tested pigs of these two breeds, raised in standard conditions. The label-free LC-MS method captured a total of 501 proteins of which 200 were subsequently considered in the between breeds comparison. A statistical pipeline based on the sparse Partial Least Squares Discriminant Analysis (sPLS-DA), coupled with stability and significance tests, was applied for the identification of up or down regulated proteins between breeds. This analysis revealed a total of 25 proteins clearly separating Italian Duroc and Italian Large White pigs. Among the top proteins differentiating the two breeds, 3-ketoacyl-CoA thiolase, mitochondrial (ACAA2) and histone H2B type 2-F (HIST2H2BF) were up-regulated in Italian Duroc pigs and carboxylesterase 3 (CES3) and ketohexokinase (KHK) were up-regulated in Italian Large White pigs. Fatty acid synthase (FASN), involved in fatty acid metabolism and encoded by a gene located in a QTL region for fatty acid composition, was up-regulated in Italian Large White pigs. The in silico protein interaction analysis showed that 16 of these proteins were connected in one big module. Bioinformatic functional analysis indicated that differentially expressed proteins were involved in several biological processes related to the metabolism of lipids, amino-acids, carbohydrates, cofactors and antibiotics/drugs, suggesting that these functions might distinguish Italian Duroc and Italian Large White pigs. This pilot comparative proteomic analysis of the porcine liver highlighted several biological factors that could determine the peculiar production potentials of these two heavy pig breeds, derived by their different genetic backgrounds.

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Comparative analysis of immune related genes between domestic pig and germ-free minipig.

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Comparative analysis of immune related genes between domestic pig and germ-free minipig.

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