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Research Pediatrics
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. UMCG Research

Team:

Published genetically engineered mouse models (GEMMs)

ATVB 2022
ATVB 2022

Dyonne Y Vos, Melinde Wijers, Marieke Smit, Nicolette Huijkman, Niels J Kloosterhuis , Justina C Wolters, Joël J Tissink , Amanda C M Pronk, Sander Kooijman , Patrick C N Rensen , Jan Albert Kuivenhoven , Bart van de Sluis Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins Affiliations expand PMID: 36353989 DOI: 10.1161/ATVBAHA.122.318169 [Pubmed]

Hepatology 2022
Hepatology 2022

van Zwol W, Rimbert A, Wolters JC, Smit M, Bloks VW, Kloosterhuis NJ, Huijkman NCA, Koster MH, Tharehalli U, de Neck SM, Bournez C, Fuh MM, Kuipers J, Rajan S, de Bruin A, Ginsberg HN, van Westen GJP, Hussain MM, Scheja L, Heeren J, Zimmerman P, van de Sluis B, Kuivenhoven JA. Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion. Hepatology. 2022 Sep 2. doi: 10.1002/hep.32709. [Pubmed]

FASEB Journal 2022
FASEB journal 2022

D. Nakladal,S. P. H. Lambooy,S. Mišúth,D. Čepcová,C. P. Joschko,A. van Buiten,M. Goris,F. Hoogstra-Berends,N. J. Kloosterhuis,N. Huijkman,B. van de Sluis,G. F. Diercks,J. H. Buikema,R. H. Henning,L. E. Deelman. Homozygous whole body Cbs knockout in adult mice features minimal pathology during ageing despite severe homocysteinemiaFirst published: 22 March 2022 https://doi.org/10.1096/fj.202101550R [Pubmed]

Scientific Reports 2022
Scientific Reports 2022

Blankestijn M, Bloks VW, Struik D, Huijkman N, Kloosterhuis N, Wolters JC, Wanders RJA, Vaz FM, Islinger M, Kuipers F, van de Sluis B, Groen AK, Verkade HJ, Jonker JW. Mice with a deficiency in Peroxisomal Membrane Protein 4 (PXMP4) display mild changes in hepatic lipid metabolism. Sci Rep. 2022 Feb 15;12(1):2512. doi: 10.1038/s41598-022-06479-y. [Pubmed]

Hepatology 2021
Hepatology 2021

Rutten MGS, Derks TGJ, Huijkman NCA, Bos T, Kloosterhuis NJ, van de Kolk KCWA, Wolters JC, Koster MH, Bongiovanni L, Thomas RE, de Bruin A, van de Sluis B, Oosterveer MH. Modeling Phenotypic Heterogeneity of Glycogen Storage Disease Type 1a Liver Disease in Mice by Somatic CRISPR/CRISPR-associated protein 9-Mediated Gene Editing. Hepatology. 2021 Nov;74(5):2491-2507. doi: 10.1002/hep.32022.  [Pubmed]

CMGH 2020
CMGH 2020

JF. de Boer, H.D. de Vries, A. Palmiotti, R. Li, M. Doestzada, J.A. Hoogerland, J. Fu, A.M. La Rose, M. Westerterp, N.L. Mulder, M.V. Hovingh, M. Koehorst, N.J. Kloosterhuis, J.C. Wolters, V.W. Bloks, J.T. Haas, D. Dombrowicz, B. Staels, B. van de Sluis, F. Kuipers. Cholangiopathy and biliary fibrosis in Cyp2c70-deficient mice are fully reversed by ursodeoxycholic acid. CMGH 2020 Dec 11 doi.org/10.1016/j.jcmgh.2020.12.004 [Pubmed]

Nat Comm 2020
Nat Comm 2020

Loregger A, Raaben M, Nieuwenhuis J, Tan JME, Jae LT, van den Hengel LG, Hendrix S, van den Berg M, Scheij S, Song JY, Huijbers IJ, Kroese LJ, Ottenhoff R, van Weeghel M, van de Sluis B, Brummelkamp T, Zelcer N. Nat Commun. 2020 Feb 28;11(1):1128. doi: 10.1038/s41467-020-14811-1 [PubMed]

ATVB2020
ATVB2020

Loaiza N, Hartgers ML, Reeskamp LF, Balder JW, Rimbert A, Bazioti V, Wolters JC, Winkelmeijer M, Jansen HPG, Dallinga-Thie GM, Volta A, Huijkman N, Smit M, Kloosterhuis N, Koster M, F Svendsen A, van de Sluis B, Hovingh GK, Grefhorst A, Kuivenhoven JA. Arterioscler Thromb Vasc Biol. 2020 Jan 30:ATVBAHA119313470. doi: 10.1161/ATVBAHA.119.313470 [PubMed]

JLR 2019
JLR 2019

de Boer JF, Verkade E, Mulder NL, de Vries HD, Huijkman NC, Koehorst M, Boer T, Wolters JC, Bloks VW, van de Sluis B, Kuipers F. A Human-like Bile Acid Pool Induced by Deletion of Cyp2c70 Modulates Effects of Farnesoid X Receptor Activation in Mice. J Lipid Res. 2019 Sep 10. pii: jlr.RA119000243. doi: 10.1194/jlr.RA119000243 [PubMed]

Shock 2018
Shock 2018

Jongman RM, Zwiers PJ, van de Sluis B, van der Laan M, Moser J, Zijlstra JG, Dekker D, Huijkman N, Moorlag HE, Popa ER, Molema G, van Meurs M. Partial Deletion of Tie2 Affects Microvascular Endothelial Responses to Critical Illness in a Vascular Bed and Organ-Specific Way. Shock. 2018 Jul 30. doi: 10.1097/SHK.0000000000001226.  [PubMed]

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: 1x conditional knockout models; 1x transgenic models, 2x CRISPR-mediated (conditional) knockout models, 1x CRISPR-mediated knocking model, and >10 CRISPR-mediated somatic genome edited models.

Last modified:15 November 2022 09.53 a.m.