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High-resolution rodent ultrasound system for guided in utero injection and electroporation

English title High-resolution rodent ultrasound system for guided in utero injection and electroporation
Applicant Zeilhofer Hanns Ulrich
Number 150770
Funding scheme R'EQUIP
Research institution Institut für Pharmakologie und Toxikologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.12.2013 - 30.11.2014
Approved amount 70'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Embryology, Developmental Biology

Keywords (4)

spinal cord; in utero electroporation; sensory processing; genetic manipulation

Lay Summary (German)

Lead
Fortschritte in unserem Verständnis der Entwicklung und Funktion des Nervensystems hängen zu einem grossen Teil davon ab, die Expression von Genen manipulieren zu können. Klassischer Weise wird dazu das Genom in Stammzellen von Mäusen gezielt verändert. Das in diesem Projekt beantragte Gerät erlaubt es, genetisches Material in das zentrale Nervensystem von ungeborenen, noch in der Entwicklung befindlichen, Mäusen mit hoher Präzision zu injizieren.
Lay summary

Die Ultraschall-gesteuerte Injektion von genetischem Material soll in den nächsten Jahren in folgenden Forschungsprojekten zum Einsatz kommen:

Schmerzforschung: Wie kontrollieren bestimmte Typen von Nervenzellen die Schmerzleitung im Rückenmark?

Neurodegenerative Erkrankungen: Was sind die molekularen Mechanismen durch die Prionen Nervenzellen absterben lassen?

Chronobiologie: Wie kontrolliert ein kleiner Kern des Gehirns unseren Schlaf/Wachrhythmus?

Entwicklung und Plastizität hemmender Synapsen: Wie werden Rezeptoren für hemmende Überträgerstoffe in Nervenzellen reguliert?

Experimentelle Augenheilkunde: Welche ultrastrukturellen Veränderungen in der Netzhaut treten bei Erkrankungen auf, die zur Erblindung führen.

Direct link to Lay Summary Last update: 08.11.2013

Responsible applicant and co-applicants

Publications

Publication
Binary recombinase systems for high-resolution conditional mutagenesis
Hermann M, Stillhard P, Wildner H, Seruggia D, Kapp V, Sánchez-Iranzo H, Pelczar P, Binary recombinase systems for high-resolution conditional mutagenesis, in Nucleic Acids Res, 42(6), 3894-3907.

Collaboration

Group / person Country
Types of collaboration
Fritjof Helmchen/Brain Research Institute, University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Carmen Birchmeier/MDC Berlin Germany (Europe)
- Publication
Pawel Pelczar Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
133043 Blinding Diseases of the Retina: Molecular Signaling and Neuroprotection 01.01.2011 Project funding
146120 Signaling complexes associated with GABAergic synapses and their relevance for the regulation of adult neurogenesis 01.06.2013 Project funding
147111 Molecules and genes controlling diurnal behavior and physiology 01.04.2013 Project funding
141193 The prion protein in health and disease 01.06.2012 Project funding

Abstract

We request here a high-resolution ultrasound instrument for locally precise in utero injections of plasmids and viruses into early stage mouse embryos for fast genetic manipulation. Gene targeting in mice has become one of the most powerful techniques in many areas of biology in particular in studies addressing the development and function of the mammalian CNS. Most of these studies rely on gene targeting in embryonic mouse stem cells and the subsequent establishment of transgenic mouse lines. Although it is still the gold-standard, this approach is very time consuming, expensive and does usually not allow the screening of larger numbers of different constructs. In utero electroporation of mouse embryos is a meanwhile well-established alternative method. It does not allow the establishment of transgenic mouse lines, but permits fast generation of genetically modified mice within a few weeks. It also allows the simultaneous introduction of multiple transgenes (including constructs for gene know-down experiments), and is also suitable for the in vivo screening of many different constructs. In later-stage embryos, the necessary injections can be made with relatively simple surgical microscopes, but early-stage embryos require more sophisticated visualization techniques. The spatial resolution of recently developed ultrasound instruments has meanwhile reached a level that fulfills the requirements needed for in utero injection of such early-stage embryos. The instrument requested here shall be established at the Institute of Pharmacology and Toxicology of the University of Zurich. It will be specifically dedicated to in utero injections of mouse embryos and will be used primarily by groups working on the development or function of the CNS. The most extensive use is foreseen by three groups of the Institute of Pharmacology and Toxicology and by the Institute for Neuropathology. The main projects that will greatly benefit from the new instrument are (1) the morphological and functional characterization of newly identified subpopulations of dorsal horn interneurons (Zeilhofer/Wildner), (2) generation of inducible prion protein (Prp) intein transgenic mice (Aguzzi), (3) genetic manipulation of central circadian pacemakers (Brown/Dallmann (4) the role of gephyrin and collybistin in the formation and plasticity of inhibitory synapses (Fritschy/Tyagarajan), (5) genetic manipulation of photoreceptors in the retina (Grimm) (6) the in vivo testing of new constructs for cross-sectional gene targeting (Pelzcar/Wildner). In addition, the instrument will be made available to all other interested groups at UZH on a collaborative basis.
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