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Tissues Expression, Polymorphisms Identification of FcRn Gene and Its Relationship with Serum Classical Swine Fever Virus Antibody Level in Pigs

  • Liu, Yang (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Wang, Chonglong (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Liu, Zhengzhu (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Xu, Jingen (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Fu, Weixuan (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Wang, Wenwen (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Ding, Xiangdong (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Liu, Jianfeng (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University) ;
  • Zhang, Qin (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
  • Received : 2012.01.08
  • Accepted : 2012.05.17
  • Published : 2012.08.01

Abstract

Neonatal Fc receptor (FcRn) gene encodes a receptor that binds the Fc region of monomeric immunoglobulin G (IgG) and is responsible for IgG transport and stabilization. In this report, the 8,900 bp porcine FcRn genomic DNA structure was identified and putative FcRn protein included 356 amino acids. Alignment and phylogenetic analysis of the porcine FcRn amino acid sequences with their homologies of other species showed high identity. Tissues expression of FcRn mRNA was detected by real time quantitative polymerase chain reaction (Q-PCR), the results revealed FcRn expressed widely in ten analyzed tissues. One single nucleotide polymorphism (SNP) (HQ026019:g.8526 C>T) in exon6 region of porcine FcRn gene was demonstrated by DNA sequencing analysis. A further analysis of SNP genotypes associated with serum Classical Swine Fever Virus antibody (anti-CSFV) concentration was performed in three pig populations including Large White, Landrace and Songliao Black pig (a Chinese indigenous breed). Our results of statistical analysis showed that the SNP had a highly significant association with the level of anti-CSFV antibody (At d 20; At d 35) in serum (p = 0.008; p = 0.0001). Investigation of expression and polymorphisms of the porcine FcRn gene will help us in further understanding the molecular basis of the antibody regulation pathway in the porcine immune response. All these results indicate that FcRn gene might be regarded as a molecular marker for genetic selection of anti-CSFV antibody level in pig disease resistance breeding programmes.

Keywords

References

  1. Borvak, J., J. Richardson, C. Medesan, F. Antohe, C. Radu, M. Simionescu, V. Ghetie and E. S. Ward. 1998. Functional expression of the MHC class I-related receptor, FcRn, in endothelial cells of mice. Int. Immunol. 10:1289-1298. https://doi.org/10.1093/intimm/10.9.1289
  2. Brambell, F. 1966. The transmission of immunity from mother to young and the catabolism of immunoglobulins. The Lancet 2: 1087-1093.
  3. Capon, F., M. H. Allen, M. Ameen, A. D. Burden, D. Tillman, J. N. Barker and R. C. Trembath. 2004. A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum. Mol. Genet. 13:2361-2368. https://doi.org/10.1093/hmg/ddh273
  4. Dong, X. N. and Y. H. Chen. 2007. Marker vaccine strategies and candidate CSFV marker vaccines. Vaccine 25:205-230. https://doi.org/10.1016/j.vaccine.2006.07.033
  5. Hinton, P. R., M. G. Johlfs, J. M. Xiong, K. Hanestad, K. C. Ong, C. Bullock, S. Keller, M. T. Tang, J. Y. Tso and M. Vásquez. 2004. Engineered human IgG antibodies with longer serum half-lives in primates. J. Biol. Chem. 279:6213-6216.
  6. Hinton, P. R., J. M. Xiong, M .G. Johlfs, M. T. Tang, S. Keller and N. Tsurushita. 2006. An engineered human IgG1 antibody with longer serum half-life. J. Immunol. 176:346-356. https://doi.org/10.4049/jimmunol.176.1.346
  7. Israel, E., S. Taylor, Z. Wu, E. Mizoguchi, R. Blumberg, A. Bhan and N. Simister. 1997. Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells. Immunology 92: 69-74. https://doi.org/10.1046/j.1365-2567.1997.00326.x
  8. Jones, E. A. and T. A. Waldmann. 1972. The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J. Clin. Invest. 51:2916-2927. https://doi.org/10.1172/JCI107116
  9. Kamei, D. T., B. J. Lao, M. S. Ricci, R. Deshpande, H. Xu, B. Tidor and D. A. Lauffenburger. 2005. Quantitative methods for developing Fc mutants with extended half‐lives. Biotechnol. Bioeng. 92:748-760. https://doi.org/10.1002/bit.20624
  10. Kimchi-Sarfaty, C., J. M. Oh, I. W. Kim, Z. E. Sauna, A. M. Calcagno, S. V. Ambudkar and M. M. Gottesman. 2007. A" silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315:525-528. https://doi.org/10.1126/science.1135308
  11. Mayer, B., Z. Kis, G. Kajan, L. V. Frenyo, L. Hammarstrom and I. Kacskovics. 2004. The neonatal Fc receptor (FcRn) is expressed in the bovine lung. Vet. Immunol. Immunopathol. 98:85-89. https://doi.org/10.1016/j.vetimm.2003.10.010
  12. McCarthy, K. M., Y. Yoong and N. E. Simister. 2000. Bidirectional transcytosis of IgG by the rat neonatal Fc receptor expressed in a rat kidney cell line: a system to study protein transport across epithelia. J. Cell Sci. 113:1277-1285.
  13. Morphis, L. G. and D. Gitlin. 1970. Maturation of the maternofoetal transport system for human $\gamma$-globulin in the mouse. Nature 228:573.
  14. Petkova, S. B., S. Akilesh, T. J. Sproule, G. J. Christianson, H. Al. Khabbaz, A. C. Brown, L. G. Presta, Y. G. Meng and D. C. Roopenian. 2006. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int. Immunol. 18:1759-1769. https://doi.org/10.1093/intimm/dxl110
  15. Praetor, A., I. Ellinger and W. Hunziker. 1999. Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells. J. Cell Sci. 112:2291-2299.
  16. Raghavan, M. and P. J. Bjorkman. 1996. Fc receptors and their interactions with immunoglobulins. Annu. Rev. Cell Dev. Biol. 12:181-220. https://doi.org/10.1146/annurev.cellbio.12.1.181
  17. Roberts, D. M., M. Guenthert and R. Rodewald. 1990. Isolation and characterization of the Fc receptor from the fetal yolk sac of the rat. J. Cell Biol. 111:1867-1876. https://doi.org/10.1083/jcb.111.5.1867
  18. Roopenian, D. C. and S. Akilesh. 2007. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7:715-725. https://doi.org/10.1038/nri2155
  19. Roopenian, D. C., G. J. Christianson, T. J. Sproule, A. C. Brown, S. Akilesh, N. Jung, S. Petkova, L. Avanessian, E. Y. Choi and D. J. Shaffer. 2003. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J. Immunol. 170:3528-3533. https://doi.org/10.4049/jimmunol.170.7.3528
  20. Sambrook, J., E. F. Fritsch and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, New York, USA.
  21. Shah, U., B. L. Dickinson, R. S. Blumberg, N. E. Simister, W. I. Lencer and W. A. Walker. 2003. Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine. Pediatr. Res. 53: 295-301. https://doi.org/10.1203/00006450-200302000-00015
  22. Shields, R. L., A. K. Namenuk, K. Hong, Y. G. Meng, J. Rae, J. Briggs, D. Xie, J. Lai, A. Stadlen and B. Li. 2001. High resolution mapping of the binding site on human IgG1 for Fc$\gamma$RI, Fc$\gamma$RII, Fc$\gamma$RIII, and FcRn and design of IgG1 variants with improved binding to the Fc$\gamma$R. J. Biol. Chem. 276:6591-6604. https://doi.org/10.1074/jbc.M009483200
  23. Simister, N., I. E. Jacobowitz, J. Ahouse and C. Story. 1997. New functions of the MHC class I-related Fc receptor, FcRn. Biochem. Soc. Trans. 25:481-486.
  24. Simister, N. E. and K. E. Mostov. 1989. An Fc receptor structurally related to MHC class I antigens. Nature 337:184-187. https://doi.org/10.1038/337184a0
  25. Spiekermann, G. M., P. W. Finn, E. S. Ward, J. Dumont, B. L. Dickinson, R. S. Blumberg and W. I. Lencer. 2002. Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life. J. Exp. Med. 196:303-310. https://doi.org/10.1084/jem.20020400
  26. Vaccaro, C., J. Zhou, R. J. Ober and E. S. Ward. 2005. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat. Biotechnol. 23:1283-1288.
  27. Ward, E. S., J. Zhou, V. Ghetie and R. J. Ober. 2003. Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans. Int. Immunol. 15:187-195. https://doi.org/10.1093/intimm/dxg018

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