Infrastructure
A respiratory for genetically modified mouse lines for tissue specific gene targeting: CRE lines
A large number of transgenic mouse lines that can be used for the generation of inducible and tissue specific ?knock outs? using the Cre-loxP system under tissue specific promoters such as the lck-Cre (T-lymphoid), CD19-Cre (B-lymphoid), SCL-Cre (erythroid), CD11b-Cre (myeloid lineage cells) are collected at the IMP/IMBA; These mice will be bred and made available to other Austrian researchers.
Quality control: Josef PENNINGER, Erwin WAGNER
Archiving and rederivation of mouse mutants: SPF quality, cryopreservation in vitro fertilization
The ÖZBT will provide the generation and breeding of mouse mutants exclusive in SPF-quality, an essential prerequisite for many mouse experiments in cancer or immunology. The introduction of mice with undefined or unknown hygienic quality into the ÖZBT facilities will be performed via embryo transfer. Additionally, ÖZBT can accept germ cells or embryos instead of life animals from other laboratories to rederive genetically modified mouse lines.
Team leader: Mathias MÜLLER, Thomas RÜLICKE
Phenotyping of mouse mutants: MRI, telemetry and calorimetry
Mouse magnetic resonance imaging (MRI) will allow us to perform whole body scans of living mice over a long period of their lifespans. MRI can be also used to study heart functions or to follow the development of cancer . We will establish telemetry using implantable probes to obtain data on heart functions, heart rates, motor activity, body temperature, or circadian rhythms. Moreover, we will set up computerized calorimetry stations to analyze feeding and drinking behaviors, in vivo energy expenditure, real-time metabolic rates, or oxygen consumption. These systems will be used to characterize the basic phenotypes of mutants and analyze the effect of particular experimental treatments. To analyse the phenotypes of our tetraploid mice efficiently and on a large scale, we will make a concerted effort to develop a state-of-the art phenotyping facility. For instance, tumor development and possible metastases will be visualized using magnetic resonance imaging (MRI). The use of MRI will greatly reduce the numbers of mice we need, an essential prerequisite to implement tetraploids as novel disease models (as well as for public acceptance of such experiments). However, at the moment, MRI is clearly the most robust technology of choice that indeed allows screening of multiple mice in parallel. Moreover, most mouse experiments have defined singular endpoints, e.g. size or presence of tumors in breast tissue or inflammation of cells into a certain tissue in autoimmunity, but completely discount the effects of such diseases on the whole physiology and metabolism (telemetry, calorimetry) of mice. Thus, besides establishing novel technologies for mouse genomics, we will make major efforts to link genetic alterations with changes in general physiology and behavior. This will allow us not only to follow the primary tumors to indeed be able to study the whole breath of physiologic and behavioral changes that occur in disease. Such novel read-out systems will become the gold-standard of mouse experimentations in the future and should allow us to monitor the effects of disease processes on the whole organism.
Team leader: Josef PENNINGER, Erwin WAGNER
