Project: Research project

Project Details


Sjogren-Larsson syndrome (SLS) is an inherited disorder
characterized by congential ichthyosis, mental retardation and
spasticity. Preliminary studies show that cultured skin
fibroblasts from SLS patients have altered fatty alcohol metabolism
due to deficiency of the enzyme, fatty alcohol: NAD- oxidoreductase
(FAO). Normal fatty alcohol metabolism is poorly understood and
no information is known about the clinical effects of altered fatty
alcohol metabolism. Furthermore, human FAO has not been
characterized. A long-term objective of this proposal is to
understand normal fatty alcohol metabolism and how FAO deficiency
may lead to the clinical phenotype of SLS. We propose to investigate fatty alcohol metabolism in cultured skin
fibroblasts from normal and SLS subjects to understand the deranged
fatty alcohol metabolism in SLS. Using techniques of gas-liquid
chromatography in combination with radiochemical tracer studies,
we will investigate the regulation of fatty alcohol levels in
normal and SLS fibroblasts. FAO acitivity will be characterized
in normal human fibroblasts and compared to the residual FAO
activity in SLS cells to determine whether the FAO enzyme is
kinetically or structurally altered. We will search for genetic
heterogeneity in SLS by gene complementation analysis using the
techniques of somatic cll fusion. To uderstand fatty alcohol
metabolism in tissues with quite different FAO activities,
metabolic studies will be performed in rat hepatocytes and brain
tissue slices using radiochemnical and enzymatic techniques. The
subcellualr location of enzymes involved in fatty alcohol metabolic
pathways will be determined using methods of differential and
density-gradient centrifugation. The pathogenesis of SLS will be
investigate in rat feeding studies to establish whether tissue
fatty alcohol accumulation leads to biochemical and clinical
changes characteristic of SLS. These studies will provide
fundamental information about normal fatty alcohol metabolism and
the deranged fatty alcohol metabolism in SLS.
Effective start/end date2/1/891/31/92


  • National Institutes of Health


  • Medicine(all)


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.