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University Medical Center Groningen

Transgenic Mouse Clinic for Ageing Research

The mouse is one of the most useful animal models to study the biological function of proteins in living organisms. The mouse model is an established animal model to increase our knowledge on the pathophysiology of human diseases and to develop or improve treatment of these diseases. Many researchers at the UMCG are using transgenic mice to answer their research questions. To improve our sources for fundamental and biomedical research at the UMCG, we started a state-of-the-art mouse facility that will generate innovative mouse models. All techniques (recombineering, CRISPR/Cas9, ES cell culture, zygote injection) and equipment involved in the generation of new mouse models have been in implemented in our laboratory or in the animal facility (CDP Groningen).

We generate conditional knock-out (KO) mice by homologous recombination in embryonic stem (ES) cells followed by injection into blastocysts to create chimeric mice. In addition, full KO or knock-in (KI) mice can be generated by CRISPR/Cas9 technology. Transgenic mice expressing “new” proteins or protein variants can be made by different techniques, including microinjection of DNA into the pronuclei of fertilized eggs or by electroporation of ES cells followed by selection, injection into blastocysts to create eventually chimeric mice. Recently, we are using CRISPR/Cas9 technology to edit genes in somatic cells, for example in hepatocytes of living mice. Prof. Jan van Deursen (Mayo Clinic, Rochester, MN, USA) will advice our team in the different transgenic technologies.

Team:

  • Dr. Bart van de Sluis (Project leader)
  • Nicolette Huijkman (Technician: molecular techniques, ES cell culture)
  • Marieke Smit (Technician: mouse handeling, microinjection)
  • Niels Kloosterhuis (Technician: mouse handeling, microinjection)
  • Prof. Jan van Deursen (Advisor)

Published genetically engineered mouse models (GEMMs)

Circulation Research 2018
Circulation Research 2018

Fedoseienko A, Wijers M, Wolters JC, Dekker D, Smit M, Huijkman N, Kloosterhuis N, Klug H, Schepers A, Willems van Dijk K, Levels JH, Billadeau DD, Hofker MH, van Deursen J, Westerterp M, Burstein E, Kuivenhoven JA, van de Sluis B. COMMD Family Regulates Plasma LDL Levels and Attenuates Atherosclerosis Through Stabilizing the CCC Complex in Endosomal LDLR Trafficking. Circ Res. 2018 Mar 15. pii: CIRCRESAHA.117.312004. doi: 10.1161/CIRCRESAHA.117.312004. [PubMed]

Gastroenterology 2017
Gastroenterology 2017

de Boer JF, Schonewille M, Boesjes M, Wolters H, Bloks VW, Bos T, van Dijk TH,Jurdzinski A, Boverhof R, Wolters JC, Kuivenhoven JA, van Deursen JM, Oude Elferink RPJ, Moschetta A, Kremoser C, Verkade HJ, Kuipers F, Groen AK. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice. Gastroenterology. 2017 Apr;152(5):1126-1138.e6. doi: 10.1053/j.gastro.2016.12.037. Epub 2017 Jan 5. [PubMed ]

Science Translational Medicine 2017
Science Translational Medicine 2017

van der Pol A, Gil A, Sillje HHW, Tromp J, Ovchinnikova ES, Vreeswijk-Baudoin I, Hoes M, Domian IJ, van de Sluis B, van Deursen JM, Voors AA, van Veldhuisen DJ, van Gilst WH, Berezikov E, van der Harst P, de Boer RA, Bischoff R, van der Meer P. Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH. Sci Transl Med. 2017 Nov 8;9(415). [PubMed]

BBA Molecular Cell Research 2017
BBA Molecular Cell Research 2017

Riedlinger T, Dommerholt MB, Wijshake T, Kruit JK, Huijkman N, Dekker D,Koster M, Kloosterhuis N, Koonen DPY, de Bruin A, Baker D, Hofker MH, van Deursen J, Jonker JW, Schmitz ML, van de Sluis B. NF-kB p65 serine 467 phosphorylation sensitizes mice to weight gain and TNF-a or diet-induced inflammation. Biochim Biophys Acta. 2017 Jul 16. pii: S0167-4889(17)30191-X. [PubMed]

Cardiovascular Research 2016
Cardiovascular Research 2016

Booij HG., Yu H., de Boer RA., van de Kolk CW., van de Sluis B., van Deursen JM., Van Gilst WH., Silje HH., Westerbrink RD. (2016) Overexpression of A kinase interacting protein 1 attenuates myocardial ischaemia/reperfusion injury but does not influence heart failure development. Cardiovasc. Res., 111, 217-26. [PubMed]

Molecular Cell 2016
Molecular Cell 2016

Kakkar V., Månsson C., de Mattos E., Bergink S., van der Zwaag M., van Waarde M.A.W.H., Kloosterhuis N.J., Melki R., van Cruchten R., Al-Karadaghi S., Arosio P., Dobson C.M., Knowles T.P.J., Bates G.P., van Deursen J., Linse S., van de Sluis B., Emanuelsson C., Kampinga H.H. (2016) The S/T-rich motif in the DNAJB6 chaperone delays polyglutamine aggregation and the onset of disease in a mouse model. Molecular Cell . April 12. Pii:S1097(16)00227-6. [PubMed]

Journal of Cell Biology 2015
Journal of Cell Biology 2015

Li H., Koo Y., Mao X., Sifuentes-Dominguez L., Morris L.L., Jia D., Miyata N., Faulkner R.A., van deursen J.M., Vooijs M., Billadeau D.D., van de Sluis B., Cleaver B., Burstein E. (2015) Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signalling. J. Cell Biol. 211, 605-17. [PubMed]

Brain 2015
Brain 2015

Smeets C.J., Jezierska J., Watanabe H., Duarri A., Fokkens M.R., Meijer M., Zhou Q., Yakovleva T., Boddeke E., den Dunnen W., van Deursen J., Bakalkin G., Kampinga H.H., van de Sluis B., Verbeek (2015) Elevated mutanat dynorphin A cause Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23. Brain. 138, 2537-52. [PubMed]

EMBO Molecular Medicine 2015
EMBO Molecular Medicine 2015

Cannon M.V., Silke H.H., Sijbesma J.W., Vreeswijk-Bausoin I., Ciapaite J., van de Sluis B., van Deursen J., Silva G.J., de Windt L.J., Gustafsson J.A., van der Harst P., van Gilst W.H., de Boer R.A. (2015) Cardiac LXR a protects against pathological cardia hypertrophy and dysfunction by enhancing glucose uptake and utilization. EMBO Mol. Med. 7, 1229-43. [PubMed]

Plos One 2014
Plos One 2014

Mahmud H., Candido W.M., van Genne L., Vreeswijk-Baudoin I., Yu H., van de Sluis B., van Deursen J., van Gilst W.H., Silje H.H., de Boer R.A. (2014). Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor. PLoS ONE, 25;9:e89929 [PubMed]

At this moment, the following GEMMs are being characterized: 5x conditional knockout models; 4x transgenic models, 4x CRISPR-mediated knockout models, and 2x CRISPR-mediated somatic genome edited models.

Laatst gewijzigd:27 maart 2018 14:28