Skip to main content
SpringerLink
Log in

Generation of fad2 transgenic mice that produce omega-6 fatty acids

  • Article
  • Published:
Science in China Series C: Life Sciences Aims and scope Submit manuscript

Abstract

Fatty acid desaturase-2 (FAD2) introduces a double bond in position Δ12 in oleic acid (18:1) to form linoleic acid (18:2 n-6) in higher plants and microbes. A new transgenic expression cassette, containing CMV promoter/fad2 cDNA/SV40 polyA, was constructedto produce transgenic mice. Among 63 healthy offspring, 10 founders (15.9%) integrated the cotton fad2 transgene into their genomes, as demonstrated by PCR and Southern blotting analysis. All founder mice were fertile and heterozygous fad2 female and nontransgenic littermates were used for fatty acid analysis using gas chromatography. One fad2 transgenic line showed substantial differences in the fatty acid profiles and the level of linoleic acid was increased 19% (P<0.05) in transgenic muscles compared to their nontransgenic littermates. Moreover, it exhibited an 87% and a 9% increase (P<0.05) in arachidonic acid (20:4 n-6) in muscles and liver, compared to their nontransgenic littermates. The results indicate that the plant fad2 gene can be functionally expressed in transgenic mice and may playan active role in conversion of oleic acid into linoleic acid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Marszalek J R, Lodish H F. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol, 2005, 21: 633–657, 10.1146/annurev.cellbio.21.122303.120624, 1:CAS:528:DC%2BD2MXhtlektbvF, 16212510

    Article  PubMed  CAS  Google Scholar 

  2. Kang J X. The importance of omega-6/omega-3 fatty acid ratio in cell function. The gene transfer of omega-3 fatty acid desaturase. World Rev Nutr Diet, 2003, 92: 23–36, 10.1159/000073790, 1:CAS:528:DC%2BD3sXhtVWnsLjO, 14579681

    Article  PubMed  CAS  Google Scholar 

  3. Simopoulos A P. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr, 1991, 54: 438–463, 1:CAS:528:DyaK3MXmtVKlurw%3D, 1908631

    PubMed  CAS  Google Scholar 

  4. Saeki K, Matsumoto K, Kinoshita M, et al. Functional expression of a Delta12 fatty acid desaturase gene from spinach in transgenic pigs. Proc Natl Acad Sci USA, 2004, 101: 6361–6366, 10.1073/pnas.0308111101, 1:CAS:528:DC%2BD2cXjvVyitrY%3D, 15067141

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Niemann H. Transgenic pigs expressing plant genes. Proc Natl Acad Sci USA, 2004, 101: 7211–7212, 10.1073/pnas.0402011101, 1:CAS:528:DC%2BD2cXksFaksr8%3D, 15128943

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Wang Y, An X R, Liu Q, et al. Establishment of transgenic mice integrated with gene encoding cotton omega-6 fatty acid desaturase-2. J Agri Biotechnol, 2005, 13: 207–211, 1:CAS:528:DC%2BD2MXht1akurrO

    CAS  Google Scholar 

  7. Sambrook J, Fritsch E F, Maniatis T. Molecular Cloning: A Laboratory Mannual 3th ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. 2001.

    Google Scholar 

  8. Kang J X, Wang J. A simplified method for analysis of polyunsaturated fatty acids. BMC Biochem, 2005, 6: 5, 10.1186/1471-2091-6-5, 15790399, 1:CAS:528:DC%2BD2MXksF2isrs%3D

    Article  PubMed Central  PubMed  Google Scholar 

  9. Giraldo P, Montoliu L. Size matters: Use of YACs, BACs and PACs in transgenic animals. Transgenic Res, 2001, 10: 83–103, 10.1023/A:1008918913249, 1:CAS:528:DC%2BD3MXis1Kmur0%3D, 11305364

    Article  PubMed  CAS  Google Scholar 

  10. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr, 1992, 120: S129–S138, 10.1016/S0022-3476(05)81247-8, 1:CAS:528:DyaK38XisFarsLs%3D, 1532827

    Article  PubMed  CAS  Google Scholar 

  11. Innis S M. Polyunsaturated fatty acids in human milk: An essential role in infant development. Adv Exp Med Biol, 2004, 554: 27–43, 1:CAS:528:DC%2BD2MXlvVClt7s%3D, 15384565

    Article  PubMed  CAS  Google Scholar 

  12. Madsen L, Pedersen L M, Liaset B, et al. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids. J Biol Chem, 2008, 283: 7196–7205, 10.1074/jbc.M707775200, 1:CAS:528:DC%2BD1cXivFyju7w%3D, 18070879

    Article  PubMed  CAS  Google Scholar 

  13. Morimoto K C, Van Eenennaam A L, DePeters E J, et al. Endogenous production of n-3 and n-6 fatty acids in mammalian cells. J Dairy Sci, 2005, 88: 1142–1146, 1:CAS:528:DC%2BD2MXitFygtbg%3D, 15738247, 10.3168/jds.S0022-0302(05)72780-6

    Article  PubMed  CAS  Google Scholar 

  14. Kang J X, Wang J, Wu L, et al. Transgenic mice: Fat-1 mice convert n-6 to n-3 fatty acids. Nature, 2004, 427: 504, 10.1038/427504a, 1:CAS:528:DC%2BD2cXpsFWhtA%3D%3D, 14765186

    Article  PubMed  CAS  Google Scholar 

  15. Jia Q, Lupton J R, Smith R, et al. Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice. Cancer Res, 2008, 68: 3985–3991, 10.1158/0008-5472.CAN-07-6251, 1:CAS:528:DC%2BD1cXlvVOhsr8%3D, 18483285

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Nowak J, Weylandt K H, Habbel P, et al. Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis, 2007, 28: 1991–1995, 10.1093/carcin/bgm166, 1:CAS:528:DC%2BD2sXhtFWhu77J, 17634405

    Article  PubMed  CAS  Google Scholar 

  17. Hudert C A, Weylandt K H, Lu Y, et al. Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci USA, 2006, 103: 11276–11281, 10.1073/pnas.0601280103, 1:CAS:528:DC%2BD28XnvVCmtrc%3D, 16847262

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Xia S, Lu Y, Wang J, et al. Melanoma growth is reduced in fat-1 transgenic mice: Impact of omega-6/omega-3 essential fatty acids. Proc Natl Acad Sci USA, 2006, 103: 12499–12504, 10.1073/pnas.0605394103, 1:CAS:528:DC%2BD28Xos1Onsrk%3D, 16888035

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Connor K M, SanGiovanni J P, Lofqvist C, et al. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med, 2007, 13: 868–873, 10.1038/nm1591, 1:CAS:528:DC%2BD2sXnsFWmtrw%3D, 17589522

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Lai L, Kang J X, Li R, et al. Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat Biotechnol, 2006, 24: 435–436, 10.1038/nbt1198, 1:CAS:528:DC%2BD28Xjt1Wisb4%3D, 16565727

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Almendingen K, Hostmark A T, Fausa O, et al. Familial adenomatous polyposis patients have high levels of arachidonic acid and docosa-hexaenoic acid and low levels of linoleic acid and alpha-linolenic acid in serum phospholipids. Int. J Cancer, 2007, 120: 632–637, 10.1002/ijc.22337, 1:CAS:528:DC%2BD28XhtlGqsrfF, 17096349

    Article  PubMed  CAS  Google Scholar 

  22. Polesel J, Talamini R, Montella M, et al. Linoleic acid, vitamin D and other nutrient intakes in the risk of non-Hodgkin lymphoma: An Italian case-control study. Ann Oncol, 2006, 17: 713–718, 10.1093/annonc/mdl054, 1:STN:280:DC%2BD287mslSrtg%3D%3D, 16556850

    Article  PubMed  CAS  Google Scholar 

  23. Reyes N, Reyes I, Tiwari R, et al. Effect of linoleic acid on proliferation and gene expression in the breast cancer cell line T47D. Cancer Lett, 2004, 209: 25–35, 10.1016/j.canlet.2003.12.010, 1:CAS:528:DC%2BD2cXktVClurg%3D, 15145518

    Article  PubMed  CAS  Google Scholar 

  24. Kilian M, Mautsch I, Gregor J I, et al. Influence of conjugated vs. conventional linoleic acid on liver metastasis and hepatic lipidper-oxidation in BOP-induced pancreatic cancer in Syrian hamster. Prostaglandins Leukot. Essent Fatty Acids, 2002, 67: 223–228, 10.1054/plef.2002.0422, 1:CAS:528:DC%2BD38XosVSiu7k%3D

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, 100193, China

    Qing Chen, ZhiFang Wu & KeMian Gou

  2. Blackmountain Laboratory, CSIRO Plant Industry, Canberra, Australia

    Qing Liu

  3. College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China

    ZongYi Wang

Authors
  1. Qing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ZhiFang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. ZongYi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. KeMian Gou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to KeMian Gou.

Additional information

Supported by the National Basic Research and Development Program of China (Grant No. 2004CB117500), the National Natural Science Foundation of China (Grant No. 30571332), and the National Major Special Project on New Varieties Cultivation for Transgenic Organisms (Grant No. 2008ZX08008-003)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Q., Liu, Q., Wu, Z. et al. Generation of fad2 transgenic mice that produce omega-6 fatty acids. SCI CHINA SER C 52, 1048–1054 (2009). https://doi.org/10.1007/s11427-009-0143-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-009-0143-z

Keywords

Search

Navigation