HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

HGSNAT enzyme deficiency results in accumulation of heparan sulfate in podocytes and basement membranes

Lauren Nagel1, Regiana Oliveira1, Alexey V. Pshezhetsky2 and Carlos R. Morales1

1Department of Anatomy and Cell Biology, McGill University and 2Division of Medical Genetics, Centre Hospitalière Universitaire Sainte-Justine, University of Montréal, Montréal, Quebec, Canada

Offprint requests to: Carlos R. Morales, Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. e-mail: carlos.morales@mcgill.ca


Summary. Mucopolysaccharidosis III type C is a lysosomal storage disorder caused by the accumulation of heparan sulfate in lysosomes. The disorder occurs due to Heparan Acetyl-CoA: α-glucosaminide N-acetyltransferase (HGSNAT) deficiency, an enzyme which typically catalyzes the transmembrane acetylation of heparan sulfate, a basement membrane component. When the gene encoding this enzyme is mutated, it cannot perform the processing of heparan sulfate, leading to un-acetylated heparan sulfate build-up in the lysosomes of cells, causing a storage disorder. This defect has been studied primarily in brain and liver cells, but its effect on the structural integrity of the glomerulus is poorly known. The present study focuses on the effect of Hgsnat gene inactivation and heparan sulfate toxicity on the integrity of the renal corpuscle. This cortical structure was chosen because of its abundance of basement membranes and heparan sulfate as well as the renal corpuscle's physiological importance in glomerular filtration. Light microscopy, electron microscopy, and immunocytochemistry of genetically modified mice revealed a buildup of lysosomes in the podocytes, suggesting that these cells are responsible for the processing of glomerular basement membranes. Histol Histopathol 34, 1377-1385 (2019)

Key words: Heparan sulfate, Lysosome, HGSNAT, Renal corpuscle, Podocyte

DOI: 10.14670/HH-18-131