Wolfgang Wurst
Genome Engineering
Prof. Dr. Wolfgang Wurst
Group Leader (provisional)
Ingolstädter Landstr. 1
85764  Oberschleißheim-Neuherberg

wolfgang.wurst@dzne.de
 +49 89 3187-4111

Areas of investigation/research focus

Mouse models allow basic insights into the development and the progression of neurodegenerative diseases and therefore provide the opportunity to screen for effects of disease triggering genetic factors and of innovative therapeutic approaches in the entire organism. They are required for the solid and rapid preclinical translation of novel knowledge of basic research and the development of therapeutic concepts. Thus, these models are vital for molecular, physiological and behavioral dissection of neurodegenerative diseases. Hence the “Genome Engineering” Unit has the task to generate new, state-of-the-art mouse models for dementia, frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), respectively to investigate the impact of genetic defects on phenotypes and to evaluate innovative therapeutic approaches.

 more Infos

The transgenic unit of the German Center for Neurodegenerative Diseases (DZNE) is located at the Center of Stroke and Dementia Research (CSD) in Großhadern/Munich and is organized by Dr. Benedikt Wefers. The provisional group leader is Prof. Dr. Wolfgang Wurst.

The “Genome Engineering” Unit provides a centralized facility to generate mouse models of neurodegenerative diseases in particular of frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and dementia. To generate transgenic mouse models (e.g. point mutations, null mutations, conditional inducible knock-in and knock-out mutants, and deletion mutants), standard methods like the manipulation of mouse embryonic stem cells, the establishment of germ line chimera and the latest genome editing technologies, which includes the application of TALENs and the CRISPR/Cas9 system, directly in mouse one-cell embryos, are used.

The portfolio of the unit encompasses consulting and support in the design of targeting strategies, targeting vector design, the use of ES cells or one-cell embryos, validation of established models, interpretation of results, provision of standard procedures (SOPs), and providing direct access to the EUCOMM/IKMC mouse mutant resources (Prof. Dr. W. Wurst, coordinator). Furthermore, new methods are constantly developed to easily and specifically induce somatic mutations, to improve targeting efficiency, to reduce additional, unintended mutations, and to reduce the number of animals used.

Besides the generation of new transgenic mouse lines, the Unit also provides counseling in mutant analysis in particular of molecular, histological and behavioral studies.

Key Publications

Fecher C, Trovò L, Müller SA, Snaidero N, Wettmarshausen J, Heink S, Ortiz O, Wagner I, Kühn R, Hartmann J, Karl RM, Konnerth A, Korn T, Wurst W, Merkler D, Lichtenthaler SF, Perocchi F, Misgeld T. Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nat Neurosci. 2019 Oct 01; 22:1731-1742. doi: 10.1038/s41593-019-0479-z
Xianyuan Xiang, Thomas M. Piers, Benedikt Wefers, Kaichuan Zhu, Anna Mallach, Bettina Brunner, Gernot Kleinberger, Wilbur Song, Marco Colonna, Jochen Herms, Wolfgang Wurst, Jennifer M. Pocock, Christian Haass. The Trem2 R47H Alzheimer's risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans. Molecular Neurodegeneration. 2018 Sep 05; 13 doi: 10.1186/s13024-018-0280-6
Dedic N, Kühne C, Jakovcevski M, Hartmann J, Genewsky AJ, Gomes KS, Anderzhanova E, Pöhlmann ML, Chang S, Kolarz A, Vogl AM, Dine J, Metzger MW, Schmid B, Almada RC, Ressler KJ, Wotjak CT, Grinevich V, Chen A, Schmidt MV, Wurst W, Refojo D, Deussing JM. Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety. Nat Neurosci. 2018 Jun 01; 21:803-807. doi: 10.1038/s41593-018-0151-z
Meehan TF, Conte N, West DB, Jacobsen JO, Mason J, Warren J, Chen CK, Tudose I, Relac M, Matthews P, Karp N, Santos L, Fiegel T, Ring N, Westerberg H, Greenaway S, Sneddon D, Morgan H, Codner GF, Stewart ME, Brown J, Horner N; International Mouse Phenotyping Consortium, Haendel M, Washington N, Mungall CJ, Reynolds CL, Gallegos J, Gailus-Durner V, Sorg T, Pavlovic G, Bower LR, Moore M, Morse I, Gao X, Tocchini-Valentini GP, Obata Y, Cho SY, Seong JK, Seavitt J, Beaudet AL, Dickinson ME, Herault Y, Wurst W, de Angelis MH, Lloyd KCK, Flenniken AM, Nutter LMJ, Newbigging S, McKerlie C, Justice MJ, Murray SA, Svenson KL, Braun RE, White JK, Bradley A, Flicek P, Wells S, Skarnes WC, Adams DJ, Parkinson H, Mallon AM, Brown SDM, Smedley D. Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium. Nat Genet. 2017 Aug 01; 49:1231-1238. doi: 10.1038/ng.3901
Chu VT, Weber T, Wefers B, Wurst W, Sander S, Rajewsky K, Kühn R. Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells. Nat Biotechnol. 2015 May 01; 33:543-8. doi: 10.1038/nbt.3198

Info-Hotline

Thursdays 1:30-4:30 pm

Patients +49 800-7799001

(free of charge)

Professionals +49 180-779900

(9 Cent/Min. German landline, mobile and out of Germany possibly more expensive)

Inform yourself on our website cookie-free. However, we would be pleased if you would allow us to use statistical cookies. Your browser settings regarding cookies are currently as follows:
More information can be found in our Privacy policy.