Skip to main content

27.04.2017 | Original Article | Ausgabe 5/2017

Journal of Inherited Metabolic Disease 5/2017

A novel conditional Sgsh knockout mouse model recapitulates phenotypic and neuropathic deficits of Sanfilippo syndrome

Journal of Inherited Metabolic Disease > Ausgabe 5/2017
Adeline A. Lau, Barbara M. King, Carly L. Thorsen, Sofia Hassiotis, Helen Beard, Paul J. Trim, Lauren S. Whyte, Sarah J. Tamang, Stephen K. Duplock, Marten F. Snel, John J. Hopwood, Kim M. Hemsley
Wichtige Hinweise
Communicated by: Carla E. Hollak

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10545-017-0044-4) contains supplementary material, which is available to authorized users.


Mucopolysaccharidosis (MPS) type IIIA, or Sanfilippo syndrome, is a neurodegenerative lysosomal storage disorder caused by a deficiency of the lysosomal enzyme N-sulfoglucosamine sulfohydrolase (SGSH), involved in the catabolism of heparan sulfate. The clinical spectrum is broad and the age of symptom onset and the degree of preservation of cognitive and motor functions appears greatly influenced by genotype. To explore this further, we generated a conditional knockout (Sgsh KO ) mouse model with ubiquitous Sgsh deletion, and compared the clinical and pathological phenotype with that of the spontaneous Sgsh D31N MPS-IIIA mouse model. Phenotypic deficits were noted in Sgsh KO mice prior to Sgsh D31N mice, however these outcomes did not correlate with any shift in the time of appearance nor rate of accumulation of primary (heparan sulfate) or secondary substrates (GM2/GM3 gangliosides). Other disease lesions (elevations in lysosomal integral membrane protein-II expression, reactive astrocytosis and appearance of ubiquitin-positive inclusions) were also comparable between affected mouse strains. This suggests that gross substrate storage and these neuropathological markers are neither primary determinants, nor good biomarkers/indicators of symptom generation, confirming similar observations made recently in MPS-IIIA patients. The Sgsh KO mouse will be a useful tool for elucidation of the neurological basis of disease and assessment of the clinical efficacy of new treatments for Sanfilippo syndrome.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

e.Med Interdisziplinär

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf

Jetzt e.Med zum Sonderpreis bestellen!

Nur für berechtigte Nutzer zugänglich
Über diesen Artikel

Weitere Artikel der Ausgabe 5/2017

Journal of Inherited Metabolic Disease 5/2017 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin