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Sabrina Schreiber, Elisabeth Petrasch-Parwez, Elke Porrmann-Kelterbaum, Eckart Förster, Jörg T. Epplen, Wanda Maria Gerding

• The \(\it {Ccdc66}\)-deficient (\(\it {Ccdc66}\)) mouse model exhibits slow progressive retinal degeneration. It is unclear whether \(\it {Ccdc66}\) protein also plays a role in the wildtype (WT; \(\it {Ccdc66}\) +/+) mouse brain and whether the lack of \(\it {Ccdc66}\) gene expression in the \(\it {Ccdc66}\) -/- mouse brain may result in morphological and behavioral alterations. \(\it {Ccdc66}\) protein expression in different brain regions of the adult WT mouse and in whole brain during postnatal development was quantified by SDS-PAGE and Western blot. \(\it {Ccdc66}\) reporter gene expression was visualized by X-gal staining. Selected brain regions were further analyzed by light and electron microscopy. In order to correlate anatomical with behavioral data, an olfactory habituation/dishabituation test was performed. \(\it {Ccdc66}\) protein was expressed throughout the early postnatal development in the WT mouse brain. In adult mice, the main olfactory bulb exhibited high \(\it {Ccdc66}\) protein levels comparable to the expression in the retina. Additionally, the \(\it {Ccdc66}\) -/- mouse brain showed robust \(\it {Ccdc66}\) reporter gene expression especially in adult olfactory bulb glomeruli, the olfactory nerve layer and the olfactory epithelium. Degeneration was detected in the \(\it {Ccdc66}\) -/- olfactory bulb glomeruli at advanced age. This degeneration was also reflected in behavioral alterations; compared to the WT, \(\it {Ccdc66}\) -/- mice spent significantly less time sniffing at the initial presentation of unknown, neutral odors and barely responded to social odors. \(\it {Ccdc66}\) -/- mice develop substantial olfactory nerve fiber degeneration and alteration of olfaction-related behavior at advanced age. Thus, the \(\it {Ccdc66}\) -/- mouse model for retinal degeneration adds the possibility to study mechanisms of central nervous system degeneration.