Transgenic Research

, Volume 14, Issue 5, pp 563–567 | Cite as

Engineering Disease Resistant Cattle

  • David M. Donovan
  • David E. Kerr
  • Robert J. Wall
Perspective

Abstract

Mastitis is a disease of the mammary gland caused by pathogens that find their way into the lumen of the gland through the teat canal. Mammary gland infections cost the US dairy industry approximately $2 billion dollars annually and have a similar impact in Europe. In the absence of effective treatments or breeding strategies to enhance mastitis resistance, we have created transgenic dairy cows that express lysostaphin in their mammary epithelium and secrete the antimicrobial peptide into milk. Staphylococcus aureus, a major mastitis pathogen, is exquisitely sensitive to lysostaphin. The transgenic cattle resist S. aureus mammary gland challenges, and their milk kills the bacteria, in a dose dependent manner. This first step in protecting cattle against mastitis will be followed by introduction of other genes to deal with potential resistance issues and other mastitis causing organisms. Care will be taken to avoid altering milk’s nutritional and manufacturing properties. Multi-cistronic constructs may be required to achieve our goals as will other strategies possibly involving RNAi and gene targeting technology. This work demonstrates the possibility of using transgenic technology to address disease problems in agriculturally important species.

Keywords

bovine disease resistance mastitis transgene 

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References

  1. Bramley, AJ, Dodd, FH 1984Reviews of the progress of dairy science: mastitis control – progress and prospectsJ Dairy Res51481512PubMedGoogle Scholar
  2. Brophy, B, Smolenski, G, Wheeler, T, Wells, DN, L’Huillier, P, Laible, G 2003Cloned transgenic cattle produce milk with higher levels of beta-casein and kappa-caseinNat Biotechnol21157162CrossRefPubMedGoogle Scholar
  3. Burvenich, C, M, V, Mehrzad, J, Diez-Fraile, A, Duchateau, L 2003Severity of E. coli mastitis is mainly determined by cow factorsVet Res34521564CrossRefPubMedGoogle Scholar
  4. Chevalier-Mariette, C, Henry, I, Montfort, L, Capgras, S, Forlani, S, Muschler, J, Nicolas, JF 2003CpG content affects gene silencing in mice: evidence from novel transgenesGenome Biol4R53CrossRefPubMedGoogle Scholar
  5. Fire, A 1999RNA-triggered gene silencingTrends Genet15358363CrossRefPubMedGoogle Scholar
  6. Gordon, K, Lee, E, Vitale, JA, Smith, AE, Westphal, H, Hennighausen, L 1987Production of human tissue plasminogen activator in transgenic mouse milkBio/Technology511831187CrossRefGoogle Scholar
  7. Gutierrez-Adan, A, Maga, EA, Meade, H, Shoemaker, CF, Medrano, JF, Anderson, GB, Murray, JD 1996Alterations of the physical characteristics of milk from transgenic mice producing bovine kappa-caseinJ Dairy Sci79791799PubMedGoogle Scholar
  8. Hammer, RE, Pursel, VG, Rexroad, CE,Jr, Wall, RJ, Bolt, DJ, Ebert, KM, Palmiter, RD, Brinster, RL 1985Production of transgenic rabbits, sheep and pigs by microinjectionNature315680683CrossRefPubMedGoogle Scholar
  9. Kerr, DE, Plaut, K, Bramley, AJ, Williamson, CM, Lax, AJ, Moore, K, Wells, KD, Wall, RJ 2001Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic miceNat Biotechnol196670CrossRefPubMedGoogle Scholar
  10. Kerro Dego, O, Dijk, JE, Nederbragt, H 2002Factors involved in the early pathogenesis of bovine Staphylococcus aureus mastitis with emphasis on bacterial adhesion and invasion A reviewVet Quart24181198Google Scholar
  11. Lindeberg, J, Usoskin, D, Bengtsson, H, Gustafsson, A, Kylberg, A, Soderstrom, S, Ebendal, T 2004Transgenic expression of Cre recombinase from the tryrosine hydroxylase locusGenesis406773CrossRefPubMedGoogle Scholar
  12. Loeffler, J, Nelson, D, Fischetti, V 2001Rapid killing of Streptococcus pneumoniae with a bacteriophage cell wall hydrolaseScience29421702172CrossRefPubMedGoogle Scholar
  13. Lund, T, Miglior, F, Dekkers, JCM, Burnside, EB 1996Genetic relationship between clinical mastitis, somatic cell count, and udder conformation in Danish HolsteinsLivest Prod Sci39243251CrossRefGoogle Scholar
  14. Maga, EA, Anderson, GB, Cullor, JS, Smith, W, Murray, JD 1998Antimicrobial properties of human lysozyme transgenic mouse milkJ Food Prot615256PubMedGoogle Scholar
  15. Mamo, W, Boden, M, Flock, JI 1994Vaccination with Staphylococcus aureus fibrinogen binding proteins (FgBPs) reduces colonisation of S. aureus in a mouse mastitis modelFEMS Immunol Med Microbiol104753CrossRefPubMedGoogle Scholar
  16. Nelson, D, Loomis, L, Fischetti, VA 2001Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzymeP Natl Acad Sci USA9841074112CrossRefGoogle Scholar
  17. Opsahl, ML, McClenaghan, M, Springbett, A, Reid, S, Lathe, R, Colman, A, Whitelaw, CB 2002Multiple effects of genetic background on variegated transgene expression in miceGenetics16011071112PubMedGoogle Scholar
  18. Paape, MJ, Mehrzad, J, Zhao, X, Detilleux, J, Burvenich, C 2002Defense of the bovine mammary gland by polymorphonuclear neutrophil leukocytesJ Mammary Gland Biol Neoplasia7109121CrossRefPubMedGoogle Scholar
  19. Palmiter, RD, Chen, HY, Brinster, RL 1982Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspringCell29701710CrossRefPubMedGoogle Scholar
  20. Pritchard, DG, Dong, S, Baker, JR, Engler, JA 2004The bifunctional peptidoglycan lysin of Streptococcus agalactieae bacteriophage B30Microbiology15020792087CrossRefPubMedGoogle Scholar
  21. Reh, WA, Maga, EA, Collette, NM, Moyer, A, Conrad-Brink, JS, Taylor, SJ, DePeters, EJ, Oppenheim, S, Rowe, JD, Bondurant, RH, Anderson, GB, Murray, JD 2004Hot Topic: Using a Stearoyl-CoA Desaturase Transgene to Alter Milk Fatty Acid CompositionJ Dairy Sci8735103514PubMedGoogle Scholar
  22. Reik, W, Collick, A, Norris, ML, Barton, SC, Surani, MA 1987Genomic imprinting determines methylation of parental alleles in transgenic miceNature328248251CrossRefPubMedGoogle Scholar
  23. Robertson, G, Garrick, D, Wu, W, Kearns, M, Martin, D, Whitelaw, E 1995Position-dependent variegation of globin transgene expression in miceProc Natl Acad Sci USA9253715375PubMedGoogle Scholar
  24. Santoso, B, Ortiz, BD, Winoto, A 2000Control of organ-specific demethylation by an element of the T-cell receptor-alpha locus control regionJ Biol Chem27519521958CrossRefPubMedGoogle Scholar
  25. Sutherland, HG, Kearns, M, Morgan, HD, Headley, AP, Morris, C, Martin, DI, Whitelaw, E 2000Reactivation of heritably silenced gene expression in miceMamm Genome11347355CrossRefPubMedGoogle Scholar
  26. Swanson, K, Gorodetsky, S, Good, L, Musgrave, D, Stelwagen, K, Farr, V, Molenaar, A 2004Expression of a beta-defensin mRNA, lingual antimicrobial peptide, in bovine mammary epithelial tissue is induced by mastitisInfect Immun7273117314CrossRefPubMedGoogle Scholar
  27. Wall, RJ, Powell, AM, Paape, MJ, Kerr, DE, Bannerman, DD, Pursel, VG, Wells, KD, Talbot, N, Hawk, HW 2005Genetically enhanced cows resist intramammary Staphylococcus aureus infectionNat Biotechnol23445451CrossRefPubMedGoogle Scholar
  28. Wang, S, Ng, TB, Chen, T, Lin, D, Wu, J, Rao, P, Ye, X 2005First report of a novel plant lysozyme with both antifungal and antibacterial activitiesBiochem Bioph Res Co327820827CrossRefGoogle Scholar
  29. Wheeler, MB, Bleck, GT, Donovan, SM 2001Transgenic alteration of sow milk to improve piglet growth and healthReprod Suppl58313324PubMedGoogle Scholar
  30. Wilson, DJ, Gonzalez, RN, Das, HH 1997Bovine mastitis pathogens in New York and Pennsylvania: prevalence and effects on somatic cell count and milk productionJ Dairy Sci8025922598PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • David M. Donovan
    • 1
  • David E. Kerr
    • 2
  • Robert J. Wall
    • 1
  1. 1.Biotechnology and Germplasm Laboratory, Agricultural Research ServiceUnited States Department of AgricultureBeltsvilleUSA
  2. 2.Department of Animal SciencesUniversity of VermontBurlingtonUSA

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