| First Author | Haston CK | Year | 1996 |
| Journal | Cancer Res | Volume | 56 |
| Issue | 11 | Pages | 2596-601 |
| PubMed ID | 8653703 | Mgi Jnum | J:33983 |
| Mgi Id | MGI:81463 | Citation | Haston CK, et al. (1996) Inheritance of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse. Cancer Res 56(11):2596-601 |
| abstractText | 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: C(57)BL/6J (fibrosis-prone phenotype) and C3Hf/Kam (fibrosis-resistant phenotype)] and (b) characterizing inheritance of the fibrosing phenotype in the F-1 (first filial) and F-2 (F-1 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 C(57)BL/6J males was 8.4 +/- 0.8% (SE) and 4.4 +/- 0.8% for females, and the C3Hf/Kam mice of either sex did not present the fibrosing lesion (mean score, 0%). Significant difference (P = 6 x 10(-6)) was measured in percentage of fibrosis between the two strains of F-1 males, but not F-1 females (P = 0.38), suggesting the presence of an X-linked factor associated with the fibrosing phenotype, From an ANOVA the X-linked factor is estimated to contribute 19% of the fibrosis phenotype. A genetic model of two or three loci controlling the fibrosing phenotype is proposed from the data of the parental, F-1, and F-2 generations, The mouse model demonstrates that susceptibility to bleomycin- induced pulmonary fibrosis is a heritable trait controlled by a few genetic loci. |
