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SPLTRAK Abstract Submission
Loss of Arl13b in olfactory sensory neurons leads to age related olfactory impairment
Jordan C. Moretta1, Warren W. Green1, Kirill Ukhanov1, Julia C. Habif1, Chao Xie1, Lian Zhang1, Cedric R. Uytingco1, Jeffrey R. Martens1
1University of Florida, Gainesville, FL, United States
2University of Florida, Gainesville, FL, United States
3University of Florida, Gainesville, FL, United States
4University of Florida, Gainesville, FL, United States
5University of Florida, Gainesville, FL, United States
6University of Florida, Gainesville, FL, United States
7University of Florida, Gainesville, FL, United States
8University of Florida, Gainesville, FL, United States

Cilia are small, microtubule-based organelles found on most cell types, which play a vital role in numerous cell functions. In primary cilia, the small GTPase Arl13b is known to regulate ciliogenesis, protein trafficking, and signaling pathways. Mutations of ARL13b can have deleterious effects leading to human ciliopathies such as Joubert syndrome. The role of Arl13b in olfactory cilia is unknown. As such, it is also unknown if Joubert syndrome shows a penetrance into the olfactory system. Therefore, our objective is to elucidate the function of Arl13b in olfactory cilia. ARL13b is expressed during post-natal development of the OE in maturing OSNs but is dramatically reduced in OMP-positive OSNs. However, the penetrance of OMP-specific knockout of ARL13b (Arl13bosnKO) in mice is observed after this window and increases with age. In 8-week old Arl13bosnKO mice both the cilia number and length were significantly decreased resulting in impaired odor sensitivity measured by EOG. Concomitantly, in the OB of 8-week old Arl13bosnKO mice we found a significant decrease of individual glomeruli size as well as a nearly 4-fold loss of TH staining with a concentric gradient of intensity for OMP immunofluorescence. These findings suggest a previously unknown function of Arl13b, expressed during a critical time window early in the development of the OE. At 6 months of age this phenotype was exacerbated by a reduction in OE thickness, number of mature OSNs, and TH bulb staining in Arl13bosnKO mice suggesting severe neurodegeneration as well. These results indicate that Joubert syndrome patients may have an exacerbated olfactory deficit with aging. Further studies will target an exact role of Arl13b in the olfactory system and ultimately define a viable strategy for gene therapy of Joubert syndrome patients.