Brief Definitive Report RESTRICTED EXPRESSION OF ECOTROPIC VIRUS BY THYMOCYTES OF LEUKEMIA-RESISTANT (AKR × NZB)F1 MICE*

The thymus has a central role in the pathogenesis of l eukemia in AKR mice. Thymectomy great ly reduces the incidence of l eukemia (1). Moreover, v i r tua l ly all t issues of AKR mice express high t i ters of Gross (ecotropic, N-tropic) virus (2), but neoplasms develop regular ly only in the thymus. The thymus of the AKR mouse is also the site of two impor tant virological changes tha t occur dur ing the preleukemic period (6 mo of age): expression of high t i ters of xenotropic virus (2) and appearance of recombinant viruses tha t arise from ecotropic and xenotropic precursors (3, 4). These recombinants accelerate the development of l eukemia when injected into AKR mice and may be the actual leukemogenic agents in this s t ra in (3, 4). Analyses of the envelope gp70 (4) and the nucleotides (5) of the recombinant viruses indicate tha t they arise from the N-tropic AKR virus and a virus with s t ruc tura l features of the xenotropic virus produced by New Zealand Black (NZB) mice. In NZB mice the expression of xenotropic vi rus is de termined by two autosomal dominant genes, Nzv-1 and Nzv-2 (6). Two autosomal dominant genes, Akv-1 and Akv-2 , determine the production of ecotropic virus in AKR mice (7). Therefore, (AKR × NZB)F1 mice would possess these four genes. Such hybrids would also be homozygous for Fv-1 n (7). Consequently, they should, l ike preleukemic AKR mice, express high t i ters of N-tropic and xenotropic viruses, and thus be susceptible to thymic leukemia. In this paper we report a tissue-specific mechanism tha t severely restr icts expression of ecotropic virus by thymocytes of (AKR × NZB)F1 mice. This phenomenon may account for the low incidence o f thymic leukemia in these animals (8).