Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Abstract
ucopolysaccharidosis 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 membrane