Send to

Choose Destination
Exp Neurol. 2017 May;291:106-119. doi: 10.1016/j.expneurol.2017.02.009. Epub 2017 Feb 9.

Progressive leukoencephalopathy impairs neurobehavioral development in sialin-deficient mice.

Author information

Laboratory of Biological Psychology, KU Leuven, Belgium. Electronic address:
HistoGeneX, Antwerp, Belgium.
Dept. Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Research and Early Development Europe, J&J Pharmaceutical Research & Development, Beerse, Belgium.
Dept. Biology, KU Leuven, Belgium.
Laboratory of Biological Psychology, KU Leuven, Belgium.


Slc17a5-/- mice represent an animal model for the infantile form of sialic acid storage disease (SASD). We analyzed genetic and histological time-course expression of myelin and oligodendrocyte (OL) lineage markers in different parts of the CNS, and related this to postnatal neurobehavioral development in these mice. Sialin-deficient mice display a distinct spatiotemporal pattern of sialic acid storage, CNS hypomyelination and leukoencephalopathy. Whereas few genes are differentially expressed in the perinatal stage (p0), microarray analysis revealed increased differential gene expression in later postnatal stages (p10-p18). This included progressive upregulation of neuroinflammatory genes, as well as continuous down-regulation of genes that encode myelin constituents and typical OL lineage markers. Age-related histopathological analysis indicates that initial myelination occurs normally in hindbrain regions, but progression to more frontal areas is affected in Slc17a5-/- mice. This course of progressive leukoencephalopathy and CNS hypomyelination delays neurobehavioral development in sialin-deficient mice. Slc17a5-/- mice successfully achieve early neurobehavioral milestones, but exhibit progressive delay of later-stage sensory and motor milestones. The present findings may contribute to further understanding of the processes of CNS myelination as well as help to develop therapeutic strategies for SASD and other myelination disorders.


Behavior; Development; Mouse model; Myelination; Oligodendrocyte lineage; Sialic acid storage disease; Sialin

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center