The University of Georgia College of Veterinary Medicine

Georgia Veterinary Scholar Program

Georgia Veterinary Scholars Program at the UGA College of Veterinary Medicine

Georgia Veterinary Scholar	Faculty Mentor

David Brown University of Georgia Class of 2007	Dr. Paige Carmichael

Characterization of central nervous system lesions in older goats with Mucopolysaccharidosis IIID

Mucopolysaccharidosis IIID (MPS IIID) is an inherited lysosomal storage disease caused by a mutation in the N-acetylglucosamine-6-sulfatase gene that affects primarily the central nervous system (CNS) and bones of humans. The only colony of non-murine animal models of this condition is housed at the University of Georgia . The colony currently consists of six female and four male Nubian/Nubian crosses that are heterozygous for the mutation. Previous studies have only examined young (<2 yrs old) homozygous goats. Both clinical signs and lesions tend to be mild and it was thought that these animals could be easily reared to adulthood. We examined brain tissue both histologically and immunohistochemically from three older (~4 yrs age) female MPS IIID-affected goats that developed a rapid onset of neurological clinical signs prior to euthanasia and compared observations to those of a younger (~1 yr age) MPS IIID-affected goat and a normal Nubian goat. Our research showed that the accumulation of glycosaminoglycans (GAGs) was increased in older goats as compared to the younger goat, and there was more white matter astrogliosis in older goats as compared to the younger goat. There was also evidence of neuronal cell loss seen in the older goats but not in the younger goat, and mild to moderate demyelination was seen in cerebrum and cerebellum of all affected goats when compared to the normal goat. We conclude that the relatively abrupt onset of neurological signs in the older goats is due to a threshold accumulation of GAGs in neurons that results in neuronal cell death. This information may not only shed light on the pathogenesis of MPS IIID in the caprine animal model, but may allow for better understanding of the disease in humans.