PhenoTec AG offers a broad spectrum of preclinical services with an emphasis on acute and chronic lung diseases, infectious diseases, immunological and morphological investigations
Allergic asthma, Acute respiratory distress syndrome (ARDS), Subacute smoke exposure, bronchitis, Chronic bronchitis and fibrosis (CPOD), Lung emphysema
There is a dramatic rise of allergic asthma and a major need of novel, non-steroidal therapeutics for asthma. We have established severe allergic asthma models in mice with viral exacerbation to test novel therapies in mice.
Acute respiratory distress syndrome (ARDS)
ARDS is major respiratory emergency requiring effective therapy. We have established an endotoxin, ozone and virus induced models in mice. We have successfully tested novel therapies.
Subacute smoke exposure, bronchitis
CPOD is a major public health issue with chronic obstructive inflammation leading to respiratory insufficiency, for which there exist no effective treatment. Cigarette smoke exposure models in part CPOD, which we have established in mice (Doz E J Immunol 2008).
Chronic bronchitis and fibrosis (CPOD)
Another experimental approach is bleomycin induced bronchitis and lung fibrosis, a model which we also have fully established (Gasse et al J Clin Invest 2007). Mice are analysed at 1 and 14 days after bleomycin administration: BAL analysis, collagen, cytokines, and histology.
CPOD with the release of protease may also lead to destruction of alveolar septae known as emphysema. We have established an experimental model of lung emphysema by the administration of protease (Couillin I in preparation). Emphysema is induced within 2 weeks and several therapeutic approaches are being tested.
- IL17 Asthma
- Inflammasome asthma
- ILC3-derived acetylcholine promotes protease-driven allergic lung pathology
- Fibrosis: from mechanisms to medicines
- Cytokine Storm
- Efficacy and safety of a novel nitric oxide generator for the treatment of T neonatal pulmonary hypertension: Experimental and clinical studies
Corona virus and Influenza may lead to acute severe pneumonia which may be fatal. Especially the emergence of the COVID-19 strain and new influenza strains such as H1N1 represents an important public health concern.
We have established a lung infection model with COVID-19 and H1N1 strain infection which causes severe lung inflammation within a few days which may lead to death of infected in hu K18ACE2 mice and Syrian hamsters. These model serve to test novel therapeutics, which inhibit exuberant lung inflammation. Novel antiviral compounds and vaccines may be tested in this model. Furthermore, we have established Rhinovirus and RSV infection.
- IL-1b in P. aeruginosa Pneumonia
- SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function
- Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development
Recent insights revealed that the microbiota of our body plays an important part in homeostasis and diseases.
Germfree (GF) mice and rats are important tools for basic and translational research, investigating metabolites and metabolism of xenobiotic. The platform has a huge capacity to breed GF mice and rats and for experimental studies.
Why to study microbiome?
Recent studies revealed that commensal microbes in the intestines and skin and other organs play an important role for homeostasis of the body in man and rodents. Changes in diversity, composition and abundance of commensals, called dysbiosis, allows the colonization of pathogens and may disrupt epithelial barriers, which may cause systemic diseases including inflammation and metabolic changes. Conversely, intestinal inflammation may cause dysbiosis and thereby enhance the disease
GF may be of interest in local or systemic inflammation with dysbiosis enhancing disease. Testing pharmacological activity of metabolites in vivo is made possible by use of GF mice. Further, xenobiotics and drugs may be metabolized by commensal bacteria, which inactivate drug metabolites.
Proposed studies using GF rodents:
A. Investigate the altered response in dysbiotic animals
The use of GF rats/mice allows evaluating the contribution of the altered microbiome in disease models such as:
Inflammation, Infection, Infection, Cancer and Metabolic disease/obesity/diabetes
Selective colonization of GF rodents
Transfer of protective microbes or metabolites, or test probiotics mixtures for potential beneficial effects upon infectious, inflammatory or stress challenges
B. Humanized rodent models
Approach: GF mice inoculated orally with microbiota from healthy human donors represent is an attractive model for investigation to mimic part of the human environment. The humanized models allow investigating the effect of metabolites, pathobionts and probiotics in a human microbial environment.
We have established murine models of human skin disease such as psoriasis, atopic dermatitis and wound healing
- Pathogenesis of fibrosis in interstitial lung disease
- Osteoarthritis year 2010 in review: pathomechanisms
- Aryl hydrocarbon receptor (Ahr)-dependent Il-22 expression by type 3 innate lymphoid cells control of acute joint inflammation
Study protocols are established. Details protocols are available on demand. Contact us