BLEOMYCIN-INDUCED LUNG INJURY ASSESSED NON-INVASIVELY AND IN SPONTANEOUSLY BREATHING MICE BY PROTON MRI: MODEL ASSESSMENT AND TARGET VALIDATION
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Babin, Anna Louise, Cannet, Catherine, Ble, Francois-Xavier, Gerard Sachot, Christelle, Takeichi, Masatoshi, Page, Clive, Sparrer, Helmut, Matsuguchi, Tetsuya and Beckmann, Nicolau (2012) BLEOMYCIN-INDUCED LUNG INJURY ASSESSED NON-INVASIVELY AND IN SPONTANEOUSLY BREATHING MICE BY PROTON MRI: MODEL ASSESSMENT AND TARGET VALIDATION. Magnetic Resonance in Medicine, 67 (2). pp. 499-509. ISSN 0740-3194
Abstract
Magnetic resonance imaging (MRI) has been used to follow the course of bleomycin-induced lung injury in mice and to investigate two knockout mouse lines with the aim of providing potential therapeutic targets. Bleomycin (0.25 mg/kg) was administered intranasally six times, once a day. MRI was carried out on spontaneously breathing animals up to day 70 after bleomycin. Neither cardiac nor respiratory gating was applied during image acquisition. A long lasting response following bleomycin has been detected by MRI in the lungs of male C57BL/6 mice. Histology showed that, from day 14-70 after bleomycin, fibrosis was the predominant component of the injury. Female C57BL/6 mice displayed a smaller response than males. Bleomycin-induced injury was significantly more pronounced in C57BL/6 than in Balb/C mice. MRI and histology demonstrated a protection against bleomycin insult in female heterozygous and male homozygous cancer Osaka thyroid kinase knockout animals. In contrast, no protection was seen in cadherin-11 knockout animals. In summary, MRI can quantify, in spontaneously breathing mice, bleomycin-induced lung injury. With the ability for repetitive measurements in the same animal, the technique is attractive for in vivo target analysis and compound profiling in this murine model.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); On personal web site or secure external website at authors institution; Publisher's version/PDF cannot be used |
| Keywords: | lung fibrosis, bleomycin,Cot, TPL2, MAP3K8 |
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| Date Deposited: | 13 Oct 2015 13:16 |
| Last Modified: | 13 Oct 2015 13:16 |
| URI: | https://oak.novartis.com/id/eprint/2920 |