Mapping of asthma susceptibility in recombinant congenic mouse strains

PhD ceremony: Mr. B.I.A. Piavaux, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Mapping of asthma susceptibility in recombinant congenic mouse strains

Promotor(s): prof. A.J.M. van Oosterhout

Faculty: Medical Sciences

Asthma is a pulmonary inflammatory disease in which patients suffer from wheezing and shortness of breath. Like all inflammatory disease it has shown to be influenced by many genes. We used recombinant congenic mouse strains to map asthma susceptibility genes on mouse chromosome 17. Recombinant congenic strains are series of strains which have inherited one or more chromosomal fragments from a donor strain and all other DNA from the background strain. First, we investigated the power of this approach for the mapping of asthma susceptibility using the CcS/Dem series. These strains show different intensities and types of asthmatic response, which indicates that this approach could successfully be used for asthma genetics. We then started to map asthma susceptibility in the Lmr series of recombinant congenic and subcongenic strains. We identified 3 strong asthma susceptibility loci, lmr1A, lmr1B and H2. Lmr1A was further fine-mapped in a F2 cross between the RC strains and their background strain. Based upon the literature, in silico SNP analysis and expression profiling, we were able to identify candidate genes in 2 of these loci: Pla2g7 in lmr1A and Apobec-2 in lmr1B. For the H2 locus different candidate genes remain. Further studies should be undertaken to investigate this. Our models were found to be a valuable tool to investigate this complex locus which, like Pla2g7, was also associated to human asthma in many studies. It also shows that genetic research in mice can generate data relevant to human.