Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis andnephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

The proto-oncogene Frat1 was originally identified as a common site of prov iral insertion in transplanted tumors of Moloney murine leukemia virus (M-M uLV)-infected E mu-Pim1 transgenic mice. Contrary to most common insertion sites implicated in mouse T cell lymphomagenesis, retroviral insertional mu tagenesis of Frat1 constitutes a relatively late event in M-MuLV-induced tu mor development, suggesting that proviral activation of Frat1 contributes t o progression of T cell lymphomas rather than their genesis, To substantiat e this notion we have generated transgenic mice that overexpress Frat1 in v arious organs, including lymphoid tissues, Frat1 trans; genic mice develop focal glomerulosclerosis and a nephrotic syndrome, but they do not exhibit an increased incidence of spontaneous lymphomas, Conversely, these mice are highly susceptible to M-MuLV-induced lymphomagenesis, and Frat/Pim1 bitran sgenic animals develop lymphomas with increased frequency compared to Pim1 transgenic littermates, These data support a role for Frat1 in tumor progre ssion.