Characterization of the tumor and ocular phenotype in transgenic line TgN3261Rpw

TgN3261Rpw is a line of transgenic mice generated at the Oak Ridge National Laboratory as part of a large scale insertional mutagenesis program under the direction of Richard P. Woychik, Ph.D. When originally screened for phenotypic abnormalities, TgN3261Rpw mice were found to have multiple ocular anomalies. The abnormalities evident on ophthalmic examination were absence of a pupillary light response, posterior synechiae, and posterior polar cataracts. As the transgenic mice aged, 28% of the mice developed abdominal distension and became moribund due to the development of histiocytic sarcomas. A small percentage of transgenic mice developed neoplastic disease in their thoracic cavities and dermis. None of the wild type mice developed these diseases. On necropsy, the mice affected by histiocytic sarcomas had hepatomegaly, splenomegaly, and lymphadenopathy, the smaller group had thickened pleurae and pericardia, and another small group had firm small nodules, large rapidly growing masses in their dermis. The tumors were diagnosed as histiocytic sarcoma or reticulum cell sarcoma, type A. Techniques used to specifically identify the cell of origin of this tumor were immunohistochemistry, enzyme cytochemistry, flow cytometry, and molecular analysis of the immunoglobulin and T-cell receptor genes. The intradermal tumors required transplant experiments into SCID mice to confirm the histiocyte as the cell of origin. The primary ocular abnormalities include anterior segment dysgenesis, persistent hyperplastic primary vitreous and persistent hyperplastic tunica vasculosa lentis, and persistent pupillary membranes. Sequella to these anomalies include posterior synechiae, detached retinas, posterior lenticonus, and posterior polar cataracts. The tumor phenotype and the ocular phenotype can hypothetically be united as an abnormality in the growth and terminal differentiation of the resident tissue macrophages due to the transgene insertion.