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

Fargol Mazaheri, Nicolas Snaidero, Gernot Kleinberger, Charlotte Madore, Anna Daria, Georg Werner, Susanne Krasemann, Anja Capell, Dietrich Trümbach, Wolfgang Wurst, Bettina Brunner, Sebastian Bultmann, Sabina Tahirovic, Martin Kerschensteiner, Thomas Misgeld, Oleg Butovsky, Christian Haass. TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. EMBO Reports. 2017 Jun 30; 18:1186-1198. doi: 10.15252/embr.201743922
Beckervordersandforth R, Ebert B, Schäffner I, Moss J, Fiebig C,..., Wurst W, et al. Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis. Neuron. 2017 Jan 01; 93:560-573.e6. doi: 10.1016/j.neuron.2016.12.017
Kuperman Y, Weiss M, Dine J, Staikin K, Golani O,..., Wurst W, et al. CRFR1 in AgRP neurons modulates sympathetic nervous system activity to adapt to cold stress and fasting. Cell Metab. 2016 Jan 01; 23:1185-99. doi: 10.1016/j.cmet.2016.04.017
Dong-Jiunn Jeffery Truong, Karin Kühner, Ralf Kühn, Stanislas Werfel, Stefan Engelhardt, Wolfgang Wurst, Oskar Ortiz. Development of an intein-mediated split-Cas9 system for gene therapy. Nucleic Acids Research. 2015 May 25; 43:6450-6458. doi: 10.1093/nar/gkv601
Janine Arloth, Ryan Bogdan, Peter Weber, Goar Frishman, Andreas Menke, Klaus V. Wagner, Georgia Balsevich, Mathias V. Schmidt, Nazanin Karbalai, Darina Czamara, Andre Altmann, Dietrich Trümbach, Wolfgang Wurst, Divya Mehta, Manfred Uhr, Torsten Klengel, Angelika Erhardt, Caitlin E. Carey, Emily Drabant Conley, Andreas Ruepp, Bertram Müller-Myhsok, Ahmad R. Hariri, Elisabeth B. Binder. Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. Neuron. 2014 Dec 31; 86:1189-1202. doi: 10.1016/j.neuron.2015.05.034

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)

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