title: Evidence for two patterns of inheritance of sensitivity to induction of lung fibrosis in mice by radiation, one of which involves two genes.
abstract: We showed previously that autosomal recessive determinants control the development of pulmonary fibrosis in mice during the early and late phases after irradiation. The extent of fibrosis was inversely correlated with the intrinsic lung activity of both plasminogen activator (PLA) and angiotensin-converting enzyme (ACE). To test these observations further, two groups of mice were given a dose of 15 Gy to the thorax: offspring of a backcross between C57L/J ("fibrosing mice") and the F1 of CBA/J ("non-fibrosing in the early phase") x C57L/J, and additional F1 individuals of CBA/J x C57L/J. Mice were euthanized upon developing a substantial respiratory deficiency (50% reduction in carbon monoxide uptake) during the early phase (14-25 weeks postirradiation). Seventeen mice from the backcross were heavily fibrosed, 38 were classed as intermediate, and 15 contained no fibrosis. No evidence of sex linkage was seen. These data strongly support our earlier conclusions and suggest that two autosomal genes which function additively determine the extent of the principal type of fibrosis in these strains. As no indication of a bimodal distribution of lung PLA or ACE activity was obtained, it is unlikely that one of the genes controls the level of either enzyme. The F1 mice unexpectedly showed small amounts of an unusual type of fibrosis which was not associated with hyaline material or fibrin deposits, in contrast to all previous reports of fibrosis during the early phase in mice. Similar, fibrin-free fibrosis was found during the early phase in mast cell-deficient WBB6F1/J mice (and their normal siblings). In the F1 mice this unusual fibrosis appears to be regulated independently by two additional genes, one of which is sex-linked.
authors.affiliation: Department of Radiobiology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Franko
authors.forename: J
authors.initials: J
authors.lastname: Sharplin
authors.forename: W F
authors.initials: WF
authors.lastname: Ward
authors.forename: J M
authors.initials: JM
authors.lastname: Taylor
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D008168:Lung / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D010960:Plasminogen Activators / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D007703:Peptidyl-Dipeptidase A; D010960:Plasminogen Activators