by Yong-Hui Jiang, 2/1/2005

We became interested in Fragile X syndrome research after identification of CYFIP1 (by J.L. Mandel’s group), an FMRP interacting protein. The CYFIP1 gene is implicated in Prader-Willi syndrome (PWS.) PWS is a genetic disorder characterized by symptoms including moderate mental retardation, behavioral problems, childhood obesity, and short statue. Interestingly, there are well documented clinical observations of a PWS-like phenotype in a subset of Fragile X patients who have a full mutation of the FMR1 gene.

Although the role of CYFIP1 in the pathogenesis of PWS remains unclear because of its complex expression pattern in cultured cells and brains, it has been suggested that deficiency of CYFIP1 may contribute to the abnormal social and communication behaviors seen in PWS patients. We propose to test the hypothesis that Fragile X syndrome and PWS may share a common molecular pathway. We have generated CYFIP1 mutant mice and propose to analyze them by 1) neuropathological studies; 2) electrophysiology studies with a focus on hippocampal long term potentiation (LTP) and long term depression (LTD), and 3) behavioral studies with a focus on hippocampal mediated learning and memory and social behaviors.

We believe that the results from studying of the CYFIP1 mutant mice will help to understand the pathogenesis of Fragile X syndrome and PWS and may shed light on developing therapeutic strategies.