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Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function

Department of Behavioral Biology, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany
Institute of Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany
Institute of Physiological Chemistry and Pathobiochemistry, Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany
Author to whom correspondence should be addressed.
Current address: German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), 12277 Berlin, Germany, and Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin, 14163 Berlin, Germany.
J. Dev. Biol. 2020, 8(3), 13;
Received: 12 June 2020 / Revised: 6 July 2020 / Accepted: 9 July 2020 / Published: 11 July 2020
(This article belongs to the Special Issue Feature Papers in Journal of Developmental Biology)
Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in Ndst1 gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. We observed that mutant mice did not show overt changes in the density or organization of Purkinje cells in the adult cerebellum, and behavioral tests also demonstrated normal cerebellar function. This suggested that postnatal Purkinje cell development and homeostasis are independent of Ndst1 function, or that impaired HS sulfation upon deletion of Ndst1 function may be compensated for by other Purkinje cell-expressed Ndst isoforms. To test the latter possibility, we additionally deleted the second Purkinje-cell expressed Ndst family member, Ndst2. This selectively abolished reproductive capacity of compound mutant female, but not male, mice, suggesting that ovulation, gestation, or female reproductive behavior specifically depends on Ndst-dependent HS sulfation in cells types that express Cre under Pcp2/L7 promotor control. View Full-Text
Keywords: Purkinje cell; heparan sulfate; extracellular matrix; knockout mouse; Ndst Purkinje cell; heparan sulfate; extracellular matrix; knockout mouse; Ndst
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Lewejohann, L.; Pallerla, S.R.; Schreiber, R.S.; Gerula, J.; Grobe, K. Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function. J. Dev. Biol. 2020, 8, 13.

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