Generation of antibody- and B cell-deficient pigs by targeted disruption of the J-region gene segment of the heavy chain locus

Transgenic Research

Volumn 20, Issue 3, 2011, Pages 625-641

  Mendicino, M ^a   Ramsoondar, J ^a   Phelps, C ^a   Vaught, T ^a   Ball, S ^a   LeRoith, T ^b   Monahan, J ^a   Chen, S ^a   Dandro, A ^a   Boone, J ^a   Jobst, P ^a   Vance, A ^a   Wertz, N ^c   Bergman, Z ^c   Sun, X ^c   Polejaeva, I ^a   Butler, J ^c   Dai, Y ^a   Ayares, D ^a   Wells, K ^a,d  

^a REVIVICOR INC   (United States)

^b VIRGINIA MARYLAND REGIONAL COLLEGE OF VETERINARY MEDICINE   (United States)

^c UNIVERSITY OF IOWA   (United States)

^d UNIVERSITY OF MISSOURI   (United States)

Author keywords

B cell and antibody deficiency; Genetically engineered animal model; Human polyclonal antibody; Humoral versus cellular immunity; Immunoglobulin heavy chain locus; Somatic cell nuclear transfer

Indexed keywords

ANTIBODY; IMMUNOGLOBULIN CLASS; IMMUNOGLOBULIN HEAVY CHAIN; POLYADENYLIC ACID;

ANIMAL; ARTICLE; B LYMPHOCYTE; BACTERIAL INFECTION; CELL CULTURE; DISEASE MODEL; EVALUATION; FIBROBLAST; GENE TARGETING; GENETIC ENGINEERING; GENETIC TRANSFECTION; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; METABOLISM; METHODOLOGY; NEWBORN; SWINE; T LYMPHOCYTE;

ANIMALS; ANIMALS, NEWBORN; ANTIBODIES; B-LYMPHOCYTES; BACTERIAL INFECTIONS; CELLS, CULTURED; DISEASE MODELS, ANIMAL; FIBROBLASTS; GENE TARGETING; GENETIC ENGINEERING; HUMANS; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN ISOTYPES; IMMUNOHISTOCHEMISTRY; POLY A; SWINE; T-LYMPHOCYTES; TRANSFECTION;

ANIMALIA; ARTERIVIRUS; BACTERIA (MICROORGANISMS); PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS; SUIDAE;

EID: 79955845549     PISSN: 09628819     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11248-010-9444-z     Document Type: Article

References (56)

1. Blom B, Spits H (2006) Development of human lymphoid cells. Annu Rev Immunol 24: 287-320.
2. Busslinger M (2004) Transcriptional control of early B cell development. Annu Rev Immunol 22: 55-79.
3. Butler JE, Sinkora M (2007) The isolator piglet: a model for studying the development of adaptive immunity. Immunol Res 39: 33-51.
4. Butler JE, Sun J, Navarro P (1996) The swine Ig heavy chain locus has a single JH and no identifiable IgD. Int Immunol 8: 1897-1904.
5. Butler JE, Sun J, Weber P, Navarro P, Francis D (2000) Antibody repertoire development in fetal and newborn piglets, III. Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues. Immunology 100: 119-130.
6. Butler JE, Sun J, Weber P, Ford SP, Rehakova Z, Sinkora J, Lager K (2001) Antibody repertoire development in fetal and neonatal piglets. IV. Switch recombination, primarily in fetal thymus, occurs independent of environmental antigen and is only weakly associated with repertoire diversification. J Immunol 167: 3239-3249.
7. Butler JE, Wertz N, Weber P, Lager KM (2008) Porcine reproductive and respiratory syndrome virus subverts repertoire development by proliferation of germline-encoded B cells of all isotypes bearing hydrophobic heavy chain CDR3. J Immunol 180: 2347-2356.
8. Butler JE, Lager KM, Splichal I, Francis D, Kacskovics I, Sinkora M, Wertz N, Sun J, Zhao Y, Brown WR, DeWald R, Dierks S, Muyldermans S, Lunney JK, McCray PB, Rogers CS, Welsh MJ, Navarro P, Klobasa F, Habe F, Ramsoondar J (2009) The piglet as a model for B cell and immune system development. Vet Immunol Immunopathol 128: 147-170.
9. Charley B, Riffault S, Van RK (2006) Porcine innate and adaptative immune responses to influenza and coronavirus infections. Ann N Y Acad Sci 1081: 130-136.
10. Cheetham S, Souza M, Meulia T, Grimes S, Han MG, Saif LJ (2006) Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs. J Virol 80: 10372-10381.
11. Chen J, Trounstine M, Alt FW, Young F, Kurahara C, Loring JF, Huszar D (1993) Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. Int Immunol 5: 647-656.
12. Chowdhury D, Sen R (2004) Regulation of immunoglobulin heavy-chain gene rearrangements. Immunol Rev 200: 182-196.
13. Dai Y, Vaught TD, Boone J, Chen SH, Phelps CJ, Ball S, Monahan JA, Jobst PM, McCreath KJ, Lamborn AE, Cowell-Lucero JL, Wells KD, Colman A, Polejaeva IA, Ayares DL (2002) Targeted disruption of the alpha 1, 3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20: 251-255.
14. Dawson H, Solano-Aguilar G, Beal M, Beshah E, Vangimalla V, Jones E, Botero S, Urban JF Jr (2009) Localized Th1-, Th2-, T regulatory cell-, and inflammation-associated hepatic and pulmonary immune responses in Ascaris suum-infected swine are increased by retinoic acid. Infect Immun 77: 2576-2587.
15. Eguchi-Ogawa T, Wertz N, Sun XZ, Puimi F, Uenishi H, Wells K, Chardon P, Tobin GJ, Butler JE (2010) Antibody repertoire development in fetal and neonatal piglets. XI. The relationship of variable heavy chain gene usage and the genomic organization of the variable heavy chain locus. J Immunol 184: 3734-3742.
16. Erume J, Berberov EM, Kachman SD, Scott MA, Zhou Y, Francis DH, Moxley RA (2008) Comparison of the contributions of heat-labile enterotoxin and heat-stable enterotoxin b to the virulence of enterotoxigenic Escherichia coli in F4ac receptor-positive young pigs. Infect Immun 76: 3141-3149.
17. Forsberg EJ (2005) Commercial applications of nuclear transfer cloning: three examples. Reprod Fertil Dev 17: 59-68.
18. Goodwin CS, Armstrong JA, Marshall BJ (1986) Campylobacter pyloridis, gastritis, and peptic ulceration. J Clin Pathol 39: 353-365.
19. Gunzer F, Hennig-Pauka I, Waldmann KH, Mengel M (2003) Gnotobiotic piglets as an animal model for oral infection with O157 and non-O157 serotypes of STEC. Methods Mol Med 73: 307-327.
20. Halbur PG, Paul PS, Meng XJ, Lum MA, Andrews JJ, Rathje JA (1996) Comparative pathogenicity of nine US porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a five-week-old cesarean-derived, colostrum-deprived pig model. J Vet Diagn Invest 8: 11-20.
21. Helm RM, Furuta GT, Stanley JS, Ye J, Cockrell G, Connaughton C, Simpson P, Bannon GA, Burks AW (2002) A neonatal swine model for peanut allergy. J Allergy Clin Immunol 109: 136-142.
22. Jakobovits A, Vergara GJ, Kennedy JL, Hales JF, McGuinness RP, Casentini-Borocz DE, Brenner DG, Otten GR (1993) Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production. Proc Natl Acad Sci USA 90: 2551-2555.
23. Jonjic N, Jonjic S, Saalmuller A, Rukavina D, Koszinowski UH (1987) Distribution of T-lymphocyte subsets in porcine lymphoid tissues. Immunology 60: 395-401.
24. Jung D, Giallourakis C, Mostoslavsky R, Alt FW (2006) Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol 24: 541-570.
25. Kitamura D, Rajewsky K (1992) Targeted disruption of mu chain membrane exon causes loss of heavy-chain allelic exclusion. Nature 356: 154-156.
26. Kitamura D, Roes J, Kuhn R, Rajewsky K (1991) A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature 350: 423-426.
27. Klobasa F, Werhahn E, Butler JE (1981) Regulation of humoral immunity in the piglet by immunoglobulins of maternal origin. Res Vet Sci 31: 195-206.
28. Krakowka S, Eaton KA, Rings DM, Morgan DR (1991) Gastritis induced by Helicobacter pylori in gnotobiotic piglets. Rev Infect Dis 13(Suppl 8): S681-S685.
29. Kuroiwa Y, Kasinathan P, Matsushita H, Sathiyaselan J, Sullivan EJ, Kakitani M, Tomizuka K, Ishida I, Robl JM (2004) Sequential targeting of the genes encoding immunoglobulin-mu and prion protein in cattle. Nat Genet 36: 775-780.
30. Kuroiwa Y, Kasinathan P, Sathiyaseelan T, Jiao JA, Matsushita H, Sathiyaseelan J, Wu H, Mellquist J, Hammitt M, Koster J, Kamoda S, Tachibana K, Ishida I, Robl JM (2009) Antigen-specific human polyclonal antibodies from hyperimmunized cattle. Nat Biotechnol 27: 173-181.
31. LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112: 1570-1580.
32. Lecuit M (2007) Human listeriosis and animal models. Microbes Infect 9: 1216-1225.
33. Lonberg N, Taylor LD, Harding FA, Trounstine M, Higgins KM, Schramm SR, Kuo CC, Mashayekh R, Wymore K, McCabe JG (1994) Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature 368: 856-859.
34. Mattix ME, Zeman DH, Moeller R, Jackson C, Larsen T (2006) Clinicopathologic aspects of animal and zoonotic diseases of bioterrorism. Clin Lab Med 26: 445-489 x.
35. McNeal MM, VanCott JL, Choi AH, Basu M, Flint JA, Stone SC, Clements JD, Ward RL (2002) CD4 T cells are the only lymphocytes needed to protect mice against rotavirus shedding after intranasal immunization with a chimeric VP6 protein and the adjuvant LT(R192G). J Virol 76: 560-568.
36. Melo EO, Canavessi AM, Franco MM, Rumpf R (2007) Animal transgenesis: state of the art and applications. J Appl Genet 48: 47-61.
37. Meng XJ (2003) Swine hepatitis E virus: cross-species infection and risk in xenotransplantation. Curr Top Microbiol Immunol 278: 185-216.
38. Nicholson IC, Zou X, Popov AV, Cook GP, Corps EM, Humphries S, Ayling C, Goyenechea B, Xian J, Taussig MJ, Neuberger MS, Bruggemann M (1999) Antibody repertoires of four- and five-feature translocus mice carrying human immunoglobulin heavy chain and kappa and lambda light chain yeast artificial chromosomes. J Immunol 163: 6898-6906.
39. Phelps CJ, Ball SF, Vaught TD, Vance AM, Mendicino M, Monahan JA, Walters AH, Wells KD, Dandro AS, Ramsoondar JJ, Cooper DK, Ayares DL (2009) Production and characterization of transgenic pigs expressing porcine CTLA4-Ig. Xenotransplantation 16: 477-485.
40. Ramsoondar J, Vaught T, Ball S, Mendicino M, Monahan J, Jobst P, Vance A, Duncan J, Wells K, Ayares D (2009) Production of transgenic pigs that express porcine endogenous retrovirus small interfering RNAs. Xenotransplantation 16: 164-180.
41. Randall TD, Carragher DM, Rangel-Moreno J (2008) Development of secondary lymphoid organs. Annu Rev Immunol 26: 627-650.
42. Rogers CS, Hao Y, Rokhlina T, Samuel M, Stoltz DA, Li Y, Petroff E, Vermeer DW, Kabel AC, Yan Z, Spate L, Wax D, Murphy CN, Rieke A, Whitworth K, Linville ML, Korte SW, Engelhardt JF, Welsh MJ, Prather RS (2008a) Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 118: 1571-1577.
43. Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Hanfland RA, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB Jr, Zabner J, Prather RS, Welsh MJ (2008b) Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321: 1837-1841.
44. Saif LJ, Ward LA, Yuan L, Rosen BI, To TL (1996) The gnotobiotic piglet as a model for studies of disease pathogenesis and immunity to human rotaviruses. Arch Virol Suppl 12: 153-161.
45. Sinkora M, Butler JE (2009) The ontogeny of the porcine immune system. Dev Comp Immunol 33: 273-283.
46. Sinkora J, Rehakova Z, Samankova L, Haverson K, Butler JE, Zwart R, Boersma W (2001) Characterization of monoclonal antibodies recognizing immunoglobulin kappa and lambda chains in pigs by flow cytometry. Vet Immunol Immunopathol 80: 79-91.
47. Sinkora M, Sun J, Sinkorova J, Christenson RK, Ford SP, Butler JE (2003) Antibody repertoire development in fetal and neonatal piglets. VI. B cell lymphogenesis occurs at multiple sites with differences in the frequency of in-frame rearrangements. J Immunol 170: 1781-1788.
48. Souza M, Cheetham SM, Azevedo MS, Costantini V, Saif LJ (2007) Cytokine and antibody responses in gnotobiotic pigs after infection with human norovirus genogroup II. 4 (HS66 strain). J Virol 81: 9183-9192.
49. Tomizuka K, Shinohara T, Yoshida H, Uejima H, Ohguma A, Tanaka S, Sato K, Oshimura M, Ishida I (2000) Double trans-chromosomic mice: maintenance of two individual human chromosome fragments containing Ig heavy and kappa loci and expression of fully human antibodies. Proc Natl Acad Sci USA 97: 722-727.
50. Vincent AL, Lager KM, Ma W, Lekcharoensuk P, Gramer MR, Loiacono C, Richt JA (2006) Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States. Vet Microbiol 118: 212-222.
51. Waltz E (2006) Polyclonal antibodies step out of the shadows. Nat Biotechnol 24: 1181.
52. Wang QH, Souza M, Funk JA, Zhang W, Saif LJ (2006) Prevalence of noroviruses and sapoviruses in swine of various ages determined by reverse transcription-PCR and microwell hybridization assays. J Clin Microbiol 44: 2057-2062.
53. Welter MW, Welter CJ (1990) Evaluation of killed and modified live porcine rotavirus vaccines in cesarean derived colostrum deprived pigs. Vet Microbiol 22: 179-186.
54. Wyatt LS, Earl PL, Eller LA, Moss B (2004) Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge. Proc Natl Acad Sci USA 101: 4590-4595.
55. Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trubel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME (1996) Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med 335: 1486-1493.
56. Yuan L, Wen K, Azevedo MS, Gonzalez AM, Zhang W, Saif LJ (2008) Virus-specific intestinal IFN-gamma producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs. Vaccine 26: 3322-3331.