College of Arts & Sciences

Natasha Reddy

College of Arts & Sciences Biological Sciences

Faculty Mentor: Dr. Michael Akins Biology

Danielle DeBartolo Co-Mentor

Elucidating the Molecular Basis for Olfactory Hypersensitivity in Fragile X Mice

Fragile X syndrome (FXS) is a form of autism caused by mutations in the gene for Fragile X mental retardation protein (FMRP), a key regulator of the neuronal proteome. FXS patients are hypersensitive to sensory stimuli including odors. Past work from our lab has shown that FXS mice are also hypersensitive to odors and that this reflects at least in part differences in how odors are detected in the nose. To elucidate the molecular basis for altered odor-induced responses in the peripheral olfactory system, we conducted a mass spectrometry analysis of wild type and FXS olfactory epithelia to identify signaling proteins that might be dysregulated in the FXS nose. This analysis implicated dysregulation of proteins that carry out multiple roles including signaling, scaffolding, actin binding, and control of mitochondrial function. We are currently validating the mass spec results to identify which of these pathways are candidates to underlie changes in odor-induced responses in the nose. The results of these studies will inform our understanding of altered olfactory responses in FXS and may suggest therapeutic targets for treating this dysfunction in FXS patients.