International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 54 - IDENTIFICATION OF MULTIPLE GENETIC LOCI LINKED TO LUNG FUNCTION IN MICE

Reinhard C 1, Meyer B 3, Fuchs H 2, Stöger T 1, Eder G 1, Rüschendorf F 3, Heyder J 1, Nürnberg P 3, Hrabé de Angelis M 2, Schulz H 1

1 Institute for Inhalation Biology, GSF-Research Center for Environment and Health, Neuherberg/Munich, Germany, 2 Institute of Experimental Genetics, GSF-Research Center for Environment and Health, Neuherberg/Munich, Germany, 3 Gene Mapping Center, Max-Delbrück-Centrum, Berlin, Germany

Quantitative trait locus (QTL) linkage analysis was applied to identify chromosomal regions contributing to lung function in mice. The strains C3H/HeJ (C3) and JF1/Msf (JF1) as well as their offspring were phenotyped for the parameters total lung capacity (TLC) and dead space volume (VD) describing lung and conducting airway size, respectively, lung compliance (CL) characterizing lung elasticity as well as diffusing capacity (DCO) measuring the gas exchange. A whole genome scan in 150 animals of both the backcross (N2) and intercross (F2) progeny by use of 210 microsatellite markers revealed significant linkage results on chromosomes 5, 15, 17, and 19. All analyzed traits were significantly linked to a broad region on chromosome 15 suggesting the presence of more than one gene on chromosome 15 influencing lung function. The region of interest on chromosome 17 contains a syntenic region to human chromosome 6q27, which was recently identified to be linked to lung function in humans. Interesting candidate genes are located within the peak regions, e.g. the platelet derived growth factor beta (Pdgfb) gene and the relaxin1 (Rlx1) gene. Both genes are related to lung relevant phenotypes as was demonstrated in transgenic and knock out mouse models. Sequencing of the Rlx1 gene revealed functional polymorphisms between the two parental strains. The results of our QTL linkage analysis demonstrate that lung function in mice is influenced by multiple genetic loci located on at least 4 different chromosomes.

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