Bleomycin-induced lung injury in mice investigated by MRI: model assessment for target analysis
Anna L Babin1, Catherine Cannet, Christelle Gérard
1Global Imaging Group, Novartis Institutes for BioMedical Research, Basel, Switzerland.
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.
Insights
Magnetic resonance imaging (MRI) quantifies lung injury in mice. This study identified cancer Osaka thyroid kinase knockout mice as a potential therapeutic target for bleomycin-induced lung damage.
Area of Science:
- Pulmonary Medicine
- Medical Imaging
- Pharmacology
Background:
- Bleomycin-induced lung injury is a significant research model.
- Understanding the mechanisms and potential therapeutic targets is crucial.
Purpose of the Study:
- To utilize Magnetic Resonance Imaging (MRI) to monitor bleomycin-induced lung injury in mice.
- To investigate potential therapeutic targets by examining knockout mouse lines.
Main Methods:
- Intranasal administration of bleomycin to C57BL/6 and Balb/C mice.
- Serial MRI scans on spontaneously breathing animals up to 70 days.
- Histological analysis to confirm injury and fibrosis.
- Evaluation of cancer Osaka thyroid kinase and cadherin-11 knockout mice.
Main Results:
- MRI detected long-lasting lung injury in male C57BL/6 mice, primarily fibrosis from day 14-70.
- Female mice showed a less pronounced response compared to males.
- C57BL/6 mice exhibited more severe injury than Balb/C mice.
- Cancer Osaka thyroid kinase knockout animals (female heterozygous, male homozygous) showed protection against bleomycin.
- Cadherin-11 knockout animals did not display protection.
Conclusions:
- MRI is effective in quantifying bleomycin-induced lung injury in spontaneously breathing mice.
- The technique allows for repetitive measurements in the same animal, aiding in vivo target analysis.
- Cancer Osaka thyroid kinase knockout appears to be a promising therapeutic target for bleomycin-induced lung injury.
