Laboratory Animal Facilities and Established Animal Models Unit
Biomedical Research Foundation of the Academy of Athens
Laboratory Animal Facility
The Laboratory Animal Facility of BRFAA is located on the basement of the building with a floor of 1,800 sqm and a housing capacity for 25,000 transgenic mice, 1,000 rats, 40 rabbits and 10 swine.
The main tasks of the Facility are:
- Breeding and housing of genetically altered animals
- Breeding and housing of convention animals
- Preparation of animals to undergo experiments
- Pre- and Post- surgical veterinary care of the animals
- Continuous monitoring, and improvement of animals micro- and macro – environment
- Technical advice and veterinary support to the scientists during the design of the experiments
- Education and training of scientists and technical stuff on the correct use of laboratory animals
All animals are housed in accordance to the European Legal framework existing for the Protection of animals used for scientific purposes (European Convention123/Council of Europe and European Directive 2010/63) as well as the current Guidelines of International Organizations such as the Association for the Assessment and Accreditation of Laboratory Animal Care International-AAALAC Int., and the Federation of European Laboratory Animal Science Associations-FELASA.
All mice and rats are housed under SPF conditions, in Individual Ventilated Cages. A Building Managing System (BMS) monitors all the electromechanical equipment of the facility, 24 hours per day.
The Animal Facility implements a complete veterinary medical care programme, which includes preventive medicine, surveillance, diagnosis, treatment and control of diseases as well as veterinary care of the animals, used in experimental protocols. A health-monitoring programme is also implemented, in accordance to the guidelines issued by the Federation of European Laboratory Animal Science Associations.
The facility is registered as breeding, supplying and user establishment in accordance to the National Legislation (Presidential Decree 56/2013 in harmonization to the European Directive 2010/63), under the code numbers EL25BIObr01, EL25BIOsup02and EL25BIOexp03, respectively.
- Animal models
- Cardiovascular diseases
Zebrafish Facility – Biomedical Research Foundation of the Academy of Athens
Zebrafish as an experimental model system in Translational Research
Zebrafish embryos develop externally and are transparent, allowing for in vivo non-invasive imaging. There is a plethora of transgenic and mutant lines available that mimic most human diseases. These include reporter lines for most signaling pathways related to Human Disease.
Zebrafish has emerged as a valuable whole animal platform for various stages of drug discovery efforts such as phenotypic screenings, determinations of general and/or specific toxicity (cardiac, renal, hepatotoxicity etc) and mechanism of action studies. Pioneering work of several laboratories has shown that zebrafish embryos can be used effectively for compound screens.
The first drug candidates from such screens have now entered phase 1 and 2 clinical trials. Zebrafish has reached recognition for its potential in drug screening among European scientists. EuFishBiomed and the European Zebrafish Resource Center (EZRC) in Karlsruhe have been pivotal in establishing a European hub for high throughput chemical screens and sharing of the most useful transgenic and mutant lines.
The zebrafish lab of BRFAA http://www.bioacademy.gr/lab/beis ,www.zebrafish.gr, which also participates in the Greek Infrastructure OpenScreen-GR http://www.openscreen.aua.gr, develops zebrafish phenotype-driven screening assays as an alternative to animal experiments. Phenotypic analyses and chemical screens that are completed by day five of zebrafish embryo development are not considered animal experiments and do not fall under the protection guidelines of the directive 2010/63/EU revising directive 86/609/EEC on the protection of animals used for scientific purposes as adopted on 22 September 2010. These projects thus address the 3R principle to the fullest by using assays with embryos as Replacement for animal experimentation.
Foundation for Research and Technology Hellas – Institute of Molecular Biology and Biotechnology
FORTH-ΙΜΒΒ has generated a series of genetically engineered mouse models with tissue-specific modifications of genes involved in DNA damage repair. These models can be used to study natural as well as accelerated aging. A comprehensive series of mouse mutants harbouring defects in the highly conserved Nucleotide Excision Repair pathway (NER) have been generated that reliably mimic human progerias (e.g. Cockayne syndrome; CS, Trichothiodystrophy; TTD) and similar to patients also show premature onset of age-related pathologies. For instance, a TTD-specific XPD gene mutation, causes aging-like pathology in mice at young age, including hair greying, kyphosis, cachexia, osteoporosis and a 20-40% reduced lifespan.
Similarly, CS mice show mild progeroid features that are dramatically aggravated if combined with an XPA defect suggesting that an elevated DNA damage load greatly enhances the age-related pathology [9-11]. Various mutations in Ercc1 that plays a major role in NER cause several pathologies that strongly resemble the aging features observed in patients with defects in ERCC1-XPF. Importantly, the severity of the ERCC1 mutation correlates with the onset of pathology as well as with the reduction in lifespan of these animals, ranging from 8 weeks to 14 months. Using mice that mimic aging in an accelerated mode provides unanticipated possibilities to test interventions on aging in a short-time frame. The mouse facility at IMBB-FORTH provides access to a highly innovative preclinical platform of progeroid mice to test currently available nutraceuticals, design newly developed rationalized intervention strategies, validate available biomarkers in easily accessible fluids (urine, sera) and test developing therapies aimed at combating age-related diseases such as e.g. osteoporosis, chronic inflammation, metabolic syndrome, neurodegeneration to reduce or restore the process of ageing and extend health-span.
National Hellenic Research Foundation – Institute of Chemical Biology
At the National Hellenic Research Foundation/Institute of Chemical Biology (NHRF/ICB), the modern animal house operates in accordance with national and international standards for the and use of laboratory animals which are used in the development of cutting-edge technologies, in academia and research, in toxicity studies and in pre-clinical research in the pharmaceutical industry, as well as in education.
NHRF/ICB has established 3D spheroid cultures and mouse xenografts from human tumors. These models can be used to evaluate the predictive capacity to therapeutic response. In the era of precision oncology, the efficiency of a therapeutic protocol is not often predictable for a given tumor and patient. Preclinical in vivo and ex vivo models of patient-derived xenografts (PDX) and spheroids (PDS) are tractable, renewable and have massive potential for parallel, sequential and long term therapy experiments.
These patient-derived models may reach up to 90% prediction of the clinical responses, since they keep the original intra-tumor heterogeneity (ITH), a major resistance mechanism. The involved researchers at NHRF have all the necessary experience for the successful implementation of such projects.
This involves the transplantation of tumor obtained at the time of surgery or biopsy, unmanipulated, into recipient mice, and/or into 3D spheroid culture. The ability to drive drug resistance, as happens in a patient, allows the comparison of tumor sensitization/resistance during different selected treatment protocols in a way that is not possible in the clinic. Further, development of novel rational combinatorial therapeutic protocols of anti-cancer drugs at the preclinical stage for each individual tumor will be performed. This is expected to provide oncologists with additional evidence for the preclinical individual tumor vulnerability, which may be later be translated to efficient therapies.