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Differential involvement of the extracellular 6-O-endosulfatases Sulf1 and Sulf2 in brain development and neuronal and behavioural plasticity

Item Type:Article
Title:Differential involvement of the extracellular 6-O-endosulfatases Sulf1 and Sulf2 in brain development and neuronal and behavioural plasticity
Creators Name:Kalus, I. and Salmen, B. and Viebahn, C. and von Figura, K. and Schmitz, D. and D'Hooge, R. and Dierks, T.
Abstract:The extracellular sulfatases Sulf1 and Sulf2 remove specific 6-O-sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis. In vitro data have suggested that the two enzymes show functional redundancy. To elucidate their in vivo functions and to further address the question of a putative redundancy, we have generated Sulf1- and Sulf2-deficient mice. Phenotypic analysis of these animals revealed higher embryonic lethality of Sulf2 knockout mice, which can be associated with neuroanatomical malformations during embryogenesis. Sulf1 seems not to be essential for developmental or postnatal viability, as mice deficient in this sulfatase show no overt phenotype. However, neurite outgrowth deficits were observed in hippocampal and cerebellar neurons of both mutant mouse lines, suggesting that not only Sulf2 but also Sulf1 function plays a role in the developing nervous system. Behavioural analysis revealed differential deficits with regard to cage activity and spatial learning for Sulf1- and Sulf2-deficient mouse lines. In addition, Sulf1-specific deficits were shown for synaptic plasticity in the CA1 region of the hippocampus, associated with a reduced spine density. These results reveal that Sulf1 and Sulf2 fulfil non-redundant functions in vivo in the development and maintenance of the murine nervous system.
Keywords:Heparan Sulfate Proteoglycans, Sulf1, Sulf2, Synaptic Plasticity, Behaviour, Neurite Outgrowth, Animals, Mice
Source:Journal of Cellular and Molecular Medicine
ISSN:1582-1838
Publisher:Carol Davila University Press (Romania)
Volume:13
Number:11-12
Page Range:4505-4521
Date:November 2009
Official Publication:https://doi.org/10.1111/j.1582-4934.2008.00558.x
PubMed:View item in PubMed

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