Transgenic Services

transgenic-servicesTransgenic Mouse Facility (TMF) – Dr Andrea Bacon (TMF Manager)

Genetically modified mouse models have become an increasingly popular tool in scientific research labs worldwide. Using the techniques and expertise of the TMF it is possible for research groups within the University of Birmingham to quickly and economically derive new mouse models. To become competent in transgenic techniques can take many years thereby holding up vital projects. With the TMF this expertise is in house, readily accessible and very competitively priced. As the mice are generated within the Biomedical Services Unit there are also no delays in importing or re-deriving mouse strains once they have been generated. Andrea has over 15 years experience in transgenic technology and to date have generated multiple genetically modified mouse models using pronuclear microinjection and ES cell/blastocyst injection.

Pronuclear microinjection...

 Pronuclear microinjection consists of the injection of a DNA transgene, provided by the client, to generate a transgenic mouse strain. Using this strategy it is possible to overexpress a gene of interest or to map expression patterns using a reporter construct. The transgenic mouse facility has had success injecting both standard DNA transgenes and also BAC transgenes which allow for the insertion of much larger regions of DNA.

Embryonic stem cell injection...

Injection of genetically modified ES cells into host blastocyst stage embryos to generate Knock-out/Knock-in genetically modified mouse strains. ES cells can be generated by the client but it is becoming more common to buy genetically modified (GM) ES cells helping to save both time and money. Useful websites for available GM ES cells are;

The KO Mouse Project https://www.komp.org

The Mutant Mouse Regional Resource Centers https://www.mmrrc.org 

The TMF has also had success in generating chimeras from fibroblast derived iPS cell lines (including the derivation of fibroblasts from adult tail tips).

  • Embryo fusion
    Generation of chimeric mice from two existing mouse strains.
  • Embryo cryopreservation
    Cryopreservation and storage of embryos from individual mouse strains for insurance and also to facilitate transport of mice to other institutions.
  • ES cell derivation
    Generation of embryonic stem cells from existing mouse strains to allow in vitro manipulation/differentiation.
  • Breeding programme assistance
    Advice on all aspects of breeding, cross breeding and tissue typing.

Supplementary information

Publications...

Regulation of pituitary tumor transforming gene (PTTG) expression and phosphorylation in thyroid cells.Lewy GD, Ryan GA, Read ML, Fong JC, Poole V, Seed RI, Sharma N, Smith VE, Kwan PP, Stewart SL, Bacon A, Warfield A, Franklyn JA, McCabe CJ, Boelaert K.Endocrinology. 2013 Nov;154(11):4408-22. doi: 10.1210/en.2012-2156. Epub 2013 Jul 18.

Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment. Read ML, Lewy GD, Fong JC, Sharma N, Seed RI, Smith VE, Gentilin E, Warfield A, Eggo MC, Knauf JA, Leadbeater WE, Watkinson JC, Franklyn JA, Boelaert K, McCabe CJ. Cancer Res. 2011 Oct 1;71(19):6153-64. doi: 10.1158/0008-5472.CAN-11-0720. Epub 2011 Aug 15.

Galanin acts as a trophic factor to the central and peripheral nervous systems. Hobson SA, Bacon A, Elliot-Hunt CR, Holmes FE, Kerr NC, Pope R, Vanderplank P, Wynick D. EXS. 2010;102:25-38. Review.

An epithelial progenitor pool regulates thymus growth. Jenkinson WE, Bacon A, White AJ, Anderson G, Jenkinson EJ. J Immunol. 2008 Nov 1;181(9):6101-8. Circ Res. 2008 Mar 14;102(5):554-61. doi: 10.1161/CIRCRESAHA.105.162628. Epub 2008 Jan 10.

c-Myb-dependent smooth muscle cell differentiation. Kolodziejska KM, Noyan-Ashraf MH, Nagy A, Bacon A, Frampton J, Xin HB, Kotlikoff MI, Husain M. Circ Res. 2008 Mar 14;102(5):554-61. doi: 10.1161/CIRCRESAHA.105.162628. Epub 2008 Jan 10.

Characterization of an enhancer region of the galanin gene that directs expression to the dorsal root ganglion and confers responsiveness to axotomy. Bacon A, Kerr NC, Holmes FE, Gaston K, Wynick D. J Neurosci. 2007 Jun 13;27(24):6573-80.

Galanin acts as a neuroprotective factor to the hippocampus. Elliott-Hunt CR, Marsh B, Bacon A, Pope R, Vanderplank P, Wynick D. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5105-10. Epub 2004 Mar 23.

Transgenic overexpression of galanin in the dorsal root ganglia modulates pain-related behavior.Holmes FE, Bacon A, Pope RJ, Vanderplank PA, Kerr NC, Sukumaran M, Pachnis V, Wynick D. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6180-5. Epub 2003 Apr 29.

Transgenic over-expression of galanin in injured primary sensory neurons. Bacon A, Holmes FE, Small CJ, Ghatei M, Mahoney S, Bloom S, Wynick D. Neuroreport. 2002 Nov 15;13(16):2129-32.