Activation of the brain-specific neurogranin gene in murine T-cell lymphomas by proviral insertional mutagenesis.

Neurogranin (Nrgn) is a highly expressed brain-specific protein, which sequesters calmodulin at low Ca(2+)-levels. We report here on retroviral activation of the Nrgn gene in tumors induced by the T-cell lymphomagenic SL3-3 murine leukemia virus. We have performed a systematic expression analysis of Nrgn in various mouse tissues and SL3-3 induced T-cell tumors. This demonstrated that insertional activation of Nrgn increased RNA and protein expression levels to that observed in brain. Furthermore, elevated Nrgn expression was also observed in some T-cell tumors with no detected provirus integrations into this genomic region. The presented data demonstrate that Nrgn can be produced at high levels outside the brain, and suggest a novel oncogenic role in T-cell lymphomas in mice.