ECTOPIC EXPRESSION OF A-MYB IN TRANSGENIC MICE CAUSES FOLLICULAR HYPERPLASIA AND ENHANCED B-LYMPHOCYTE PROLIFERATION

The A-myb gene is a transcription factor that shares structural and fu nctional similarities with the v-myb oncogene, To date, v-myb is the o nly myb gene directly implicated in tumorigenesis, a property attribut ed to its transactivating ability. Recent studies have demonstrated th at A-myb, like v-myb, is a potent transcriptional activator, raising t he possibility that A-myb may also participate in oncogenesis. To test this hypothesis, we generated fusion constructs that contained the hu man A-myb cDNA under control of the mouse metallothionein promoter and the mouse mammary tumor virus long terminal repeat, These constructs were Inserted into the germ line of mice, and the functional consequen ces of ectopic A-myb expression were examined. Although transgene expr ession was detected in a wide range of tissues, abnormalities were con fined primarily to hematopoietic tissues, After a 9-month latency, A-m yb transgenic mice developed hyperplasia of the spleen and lymph nodes , Enlarged tissues contained a polyclonally expanded B lymphocyte popu lation that expressed a germinal center-cell phenotype. Transgenic B l ymphocytes showed increased DNA synthesis in response to low dose mito gen stimulation, suggesting that A-myb may contribute to hyperplasia b y increasing the rate of B cell proliferation.