Inheritance of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse (original) (raw)

Based on the range of patient responses to treatment, and on animal studies, it is hypothesized that individual variation in sensitivity to bleomycin-induced pulmonary fibrosis is controlled genetically. A genetic model has been developed by (a) establishing a distinct difference in bleomycin-induced lung damage in two inbred strains of mice [parental generation: C57BL/6J (fibrosis-prone phenotype) and C3Hf/Kam (fibrosis-resistant phenotype)] and (b) characterizing inheritance of the fibrosing phenotype in the F1 (first filial) and F2 (F1 intercross; second filial) generations derived from the parental strains. Male mice received 100 mg/kg and female mice 125 mg/kg of bleomycin via s.c. osmotic minipump. The animals were sacrificed 8 weeks after treatment or when their breathing rate indicated respiratory distress. The percentage of lung with fibrosis for each mouse was quantified with image analysis of a histological section of the left lung. The mean percentage of fibrosis for the...