Bleomycin-induced lung injury in mice investigated by MRI: model assessment for target analysis

Magn Reson Med. 2012 Feb;67(2):499-509. doi: 10.1002/mrm.23009. Epub 2011 Jun 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Alleles
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Bleomycin / toxicity*
  • Cadherins / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease
  • Image Enhancement*
  • Image Processing, Computer-Assisted*
  • Lung / drug effects*
  • Lung / pathology
  • MAP Kinase Kinase Kinases / genetics
  • Magnetic Resonance Imaging*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Proto-Oncogene Proteins / genetics
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / pathology
  • Sex Factors

Substances

  • Antibiotics, Antineoplastic
  • Cadherins
  • Proto-Oncogene Proteins
  • Bleomycin
  • osteoblast cadherin
  • MAP Kinase Kinase Kinases
  • Map3k8 protein, mouse