Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a contagious lung cancer in sheep. Previous studies have shown that the JSRV envelope protein (Env) functions as an oncogene, in that it can morphologically transform rodent fibroblast and epithelial cell lines. To obtain a small animal model for JSRV-induced OPA, we generated a transgene expressing an epitope-tagged JSRV Env under control of the lung-specific Surfactant Protein A (SPA) promoter. Transgenic mice containing the SPA-Env-HA transgene showed low efficiency but specific expression in the lung. F1 male progeny from one transgenic founder developed subdermal lipomas that expressed the transgene. These results indicate that the JSRV Env protein is capable of inducing tumors in transgenic mice, and in other cell types besides lung epithelial cells.

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer in sheep. Previous experiments in differentiated murine tissue culture cell lines suggested that the disease specificity of JSRV for secretory lung epithelial cells (type II pneumocytes an Clara cells) reflects transcriptional specificity of the viral long terminal repeat (LTR) for these cells. To test this in vivo, transgenic mice carrying the bacterial beta-galactosidase (beta-Gal) gene driven by the JSRV LTR were generated. Two transgenic lines showed beta-Gal expression in the lungs but not other tissues of F1 animals, although transgene silencing in subsequent generations was a major problem. The cells expressing the transgene were identified by two- and three-color immunofluorescence for marker proteins of type II pneumocytes (surfactant protein C [SPC]) and Clara cells (CC10) as well as for a T7 gene 10 epitope present in the beta-Gal reporter. F1 animals from both lines showed transgene expression in type II pneumocytes, but somewhat surprisingly not in Clara cells. Expression was not detected in bronchiolo-alveolar stem cells (BASCs) either. These results indicate that the JSRV LTR is specifically active in type II pneumocytes in the mouse lung, which is consistent with the fact that JSRV-induced OPA tumors in sheep largely have phenotypic markers of type II pneumocytes.