Alteration of Retinal Rod Outer Segment Membrane Fluidity in a Rat Model of Smith-Lemli-Opitz Syndrome*

Thumbnail Image
Penn collection
Departmental Papers (Dental)
Degree type
fluorescence polarization
cis-parinaric acid
fatty acid
Grant number
Copyright date
Related resources
Boesze-Battaglia, Kathleen
Damek-Poprawa, Monika
Mitchell, Drake C.
Greeley, Laura
Brush, Richard S.
Anderson, Robert E
Richards, Michael E.
Fliesler, Steven J.

Smith-Lemli-Opitz syndrome (SLOS) is caused by an inherited defect in the last step in cholesterol (Chol) biosynthesis, leading to abnormal accumulation of 7-dehydrocholesterol and decreased Chol levels. Progressive retinal degeneration occurs in an animal model of SLOS, induced by treating rats with AY9944, a selective inhibitor of the enzyme affected in SLOS. Here we evaluated alterations in the biochemical and physical properties of retinal rod outer segment (ROS) membranes in this animal model. At 1 month of AY9944 treatment, there were modest alterations in fatty acid composition, but no significant differences in cis-parinaric acid (cPA) spectroscopic parameters in ROS membranes from treated versus control rats. However, at 3 months, ROS docosahexaenoic acid (DHA) content was dramatically reduced, and cPA fluorescence anisotropy values were decreased, relative to controls. Also, 1,6-diphenyl-1,3,5-hexatriene exhibited decreased rotational motion and increased orientational order in ROS membranes from 3 month-old AY9944-treated rats, relative to controls. No significant changes in protein:lipid ratios were observed; however, rhodopsin regenerability was compromised by 3 months of treatment. These findings are consistent with reduced ROS membrane fluidity in the SLOS rat model, relative to controls, primarily due to the dramatic reduction in membrane DHA levels, rather than altered sterol composition.

Date Range for Data Collection (Start Date)
Date Range for Data Collection (End Date)
Digital Object Identifier
Series name and number
Publication date
Journal title
Journal of Lipid Research
Volume number
Issue number
Publisher DOI
Journal Issue
This research was originally published in the Journal of Lipid Research. Boesze-Battaglia, K., Damek-Poprawa, M., Mitchell, D. C., Greeley, L., Brush, R. S., Anderson, R. E., … Fliesler, S. J. (2008). Alteration of retinal rod outer segment membrane fluidity in a rat model of Smith-Lemli-Opitz syndrome. Journal of Lipid Research, 49(7), 1488–1499. © the American Society for Biochemistry and Molecular Biology
Recommended citation