To clarify the linkage between Hbb and Tls-1 (thymic
lymphoma susceptible-1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of
N-propyl-N-nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6
genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls-1 loci could be demonstrated since WKY rats also developed a high incidence of thymic
lymphomas in response to PNU. Nevertheless, thymic
lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large
tumor growth phenotype, while the [(WKY X BUF) X WKY] backcross generation consisted of rats with either rapidly growing or slowly growing
tumors. It was thus concluded that rapid development of thymic
lymphomas is determined by a gene, provisionally designated Tls-3. Analysis of the relationship between 6
genetic markers and development of thymic
lymphoma in the backcross generation demonstrated that the Tls-3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls-3 may not be identical with Tls-1 and other genes known to be relevant to
thymic tumors, but its relationship with Tls-2 remains obscure.