title: Tamoxifen dosing for Cre-mediated recombination in experimental bronchopulmonary dysplasia.
abstract: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth characterized by blunted post-natal lung development. BPD can be modelled in mice by exposure of newborn mouse pups to elevated oxygen levels. Little is known about the mechanisms of perturbed lung development associated with BPD. The advent of transgenic mice, where genetic rearrangements can be induced in particular cell-types at particular time-points during organogenesis, have great potential to explore the pathogenic mechanisms at play during arrested lung development. Many inducible, conditional transgenic technologies available rely on the application of the estrogen-receptor modulator, tamoxifen. While tamoxifen is well-tolerated and has been widely employed in adult mice, or in healthy developing mice; tamoxifen is not well-tolerated in combination with hyperoxia, in the most widely-used mouse model of BPD. To address this, we set out to establish a safe and effective tamoxifen dosing regimen that can be used in newborn mouse pups subjected to injurious stimuli, such as exposure to elevated levels of environmental oxygen. Our data reveal that a single intraperitoneal dose of tamoxifen of 0.2 mg applied to newborn mouse pups in 10 μl Miglyol vehicle was adequate to successfully drive Cre recombinase-mediated genome rearrangements by the fifth day of life, in a murine model of BPD. The number of recombined cells was comparable to that observed in regular tamoxifen administration protocols. These findings will be useful to investigators where tamoxifen dosing is problematic in the background of injurious stimuli and mouse models of human and veterinary disease.
authors.affiliation: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231, Bad Nauheim, Germany.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ruiz-Camp
authors.affiliation: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231, Bad Nauheim, Germany.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Rodríguez-Castillo
authors.affiliation: Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Herold
authors.affiliation: Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mayer
authors.affiliation: Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: István
authors.initials: I
authors.lastname: Vadász
authors.affiliation: Center for Cardiovascular Research, University of Hawaii, Honolulu, HI, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tallquist
authors.affiliation: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231, Bad Nauheim, Germany.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231, Bad Nauheim, Germany.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ahlbrecht
authors.affiliation: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231, Bad Nauheim, Germany. rory.morty@mpi-bn.mpg.de.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany. rory.morty@mpi-bn.mpg.de.
authors.forename: Rory E
authors.initials: RE
authors.lastname: Morty
mesh_terms: D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D018496:Hyperoxia / Q000235:genetics / Q000473:pathology; D019426:Integrases / Q000235:genetics*; D008168:Lung / Q000254:growth & development / Q000473:pathology; D008822:Mice, Transgenic; D010101:Oxygen Consumption / Q000235:genetics; D047928:Premature Birth / Q000235:genetics / Q000473:pathology; D011995:Recombination, Genetic; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases
keywords: Bronchopulmonary dysplasia; Hyperoxia; Lung; Tamoxifen; Transgenic