title: Bleomycin-induced lung injury in mice investigated by MRI: model assessment for target analysis.
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.
authors.affiliation: Global Imaging Group, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Babin
authors.forename: Catherine
authors.initials: C
authors.lastname: Cannet
authors.forename: Christelle
authors.initials: C
authors.lastname: Gérard
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mezard
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
authors.forename: Helmut
authors.initials: H
authors.lastname: Sparrer
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuguchi
authors.forename: Nicolau
authors.initials: N
authors.lastname: Beckmann
mesh_terms: D000281:Administration, Intranasal; D000483:Alleles; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D015820:Cadherins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D007089:Image Enhancement; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D012737:Sex Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D015820:Cadherins; D011518:Proto-Oncogene Proteins; D001761:Bleomycin; C086960:osteoblast cadherin; D020930:MAP Kinase Kinase Kinases; C489843:Map3k8 protein, mouse