关键词：果蝇；核糖核酸；抑制；染色质
摘 要：This project examines mutations found in familial cases of schwannomatosis in the tumor suppressor SMARCB1, a component of the SWI/SNF chromatin remodeling complex. Drosophila is being used to investigate the nature of the SMARCB1 mutations and the molecular consequences which give rise to schwannomas. Sensitized in vivo assays for SMARCB1 function using RNAi knockdown of Snr1 (fly ortholog of SMARCB1) reveal missense mutations from patients have varying degrees of residual function suggesting they are hypomorphic. Drosophila genetics has identified novel Snr1 interactions, including a potent interaction between Snr1 and the NF2/merlin tumor suppressor gene, which is also involved in schwannomatosis, as well as regulators of Cyclin E and the Hedgehog pathway. The consequences of SMARCB1/Snr1 knockdown on gene expression is being examined using microarrays. Purification of wild type and mutant SMARCB1 is being performed to examine altered protein interactions that may contribute to schwannomatosis.