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BLEOMYCIN-INDUCED LUNG INJURY ASSESSED NON-INVASIVELY AND IN SPONTANEOUSLY BREATHING MICE BY PROTON MRI: MODEL ASSESSMENT AND TARGET VALIDATION

Babin, Anna Louise and Cannet, Catherine and Ble, Francois-Xavier and Gerard Sachot, Christelle and Takeichi, Masatoshi and Page, Clive and Sparrer, Helmut and 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

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