Article

Molecules and Cells

, Volume 30, Issue 1, pp 13-18

First online:

Characterization of a novel mucopolysaccharidosis type II mouse model and recombinant AAV2/8 vector-mediated gene therapy

  • Sung-Chul JungAffiliated withDepartment of Biochemistry, School of Medicine, Ewha Womans University
  • , Eun-Sook ParkAffiliated withDepartment of Biochemistry, School of Medicine, Ewha Womans University
  • , Eun Nam ChoiAffiliated withDepartment of Biochemistry, School of Medicine, Ewha Womans University
  • , Chi Hwa KimAffiliated withClinical Research Center, Samsung Biomedical Research Institute
  • , Su Jin KimAffiliated withDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine
  • , Dong-Kyu JinAffiliated withDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked inherited disorder caused by a deficiency of the enzyme iduronate-2-sulfatase (IDS), which results in the lysosomal accumulation of glycosaminoglycans (GAG) such as dermatan and heparan sulfate. Here, we report the generation of IDS knockout mice, a model of human MPS II, and an analysis of the resulting phenotype. We also evaluated the effect of gene therapy with a pseudotyped, recombinant adeno-associated virus 2/8 vector encoding the human IDS gene (rAAV-hIDS) in IDS-deficient mice. IDS activity and GAG levels were measured in serum and tissues after therapy. Gene therapy completely restored IDS activity in plasma and tissue of the knockout mice. The rescued enzymatic activity completely cleared the accumulated GAGs in all the tissues analyzed. This model can be used to explore the therapeutic potential of IDS replacement and other strategies for the treatment of MPS II. Additionally, AAV2/8 vectors have promising future clinical applications for the treatment of patients with MPS II.

Keywords

adeno-associated virus gene therapy hunter syndrome iduronate-2-sulfatase MPS II mouse model