At the beginning of the study (2003), only seven of the enzymes involved in the degradation of heparan sulfate were known. Dierks and his team were searching specifically for one missing enzyme. They knew that a total of at least nine different enzymes would be needed for the complete degradation of heparan sulfate two of these (both of them sulfatases) had still not been discovered. Every inherited deficiency in one of these enzymes corresponds to a disorder belonging to the mucopolysaccharidosis syndrome. 'When we started the study, we suspected that arylsulfatase G was involved in the degradation of heparan sulfate', says Dierks. To test this assumption, his team bred mice in which arylsulfatase G was deficient. Their suspicion was confirmed: With increasing age, the mice revealed high concentrations of heparan sulfate in the brain, the liver, and the kidneys. Professor Jeffrey D. Esko from the University of California San Diego (USA) is also working in this project. He and his team analysed tissue samples with a mass spectrometer and confirmed the finding that the blocked cleavage of a specific sulfate group is the cause of the accumulation of heparan sulfate.
Using behaviour tests, Dierks's team found that mice with an ARSG deficiency suffer from cognitive problems once they reach the age of 12 months. If they enter an open field, they stick to the safer periphery and, unlike healthy littermates, do not have the courage to explore the centre. They also fail to master a water maze. For a long time, the mice had been trained successfully to swim through a pool filled with a milky liquid until they found a platform hidden beneath its surface. However, as soon as they were 12 months old, the mice failed to memorize where the platform was located. They took much longer than before to discover it. Younger and healthy mice had no
|Contact: Prof. Dr. Thomas Dierks|
University of Bielefeld