A canine model of human alpha-L-iduronidase deficiency.
AUTOR(ES)
Spellacy, E
RESUMO
A disease discovered in three Plott Hound littermates was found to be associated with a profound and specific deficiency of alpha-L-iduronidase (mucopolysaccharide alpha-L-iduronohydrolase; EC 3.2.1.76) in fibroblasts and leukocytes. The pedigree was consistent with autosomal recessive inheritance. A markedly increased amount of dermatan sulfate and heparan sulfate was excreted in urine. Fibroblasts cultured from the skin of the affected dogs accumulated excessive 35S-labeled mucopolysaccharide; this accumulation could be decreased to a normal level by exogenous human high-uptake alpha-L-iduronidase (Hurler corrective factor) as well as by secretions of normal human or canine fibroblasts. The correction was inhibited by mannose 6-phosphate. Maturation of alpha-L-iduronidase in normal canine fibroblasts followed the pathway previously observed in human fibroblasts; no cross-reactive material was observed in the cells or in secretions from the fibroblasts of the affected dogs. The canine disorder thus resembles mucopolysaccharidosis I in all biochemical parameters tested; the clinical appearance of the animals is closest to Hurler-Scheie syndrome, a form of alpha-L-iduronidase deficiency of intermediate severity. The animal model should prove valuable for therapeutic experiments.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=534366Documentos Relacionados
- Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow.
- Leucocyte values of alpha-L-iduronidase activity in mucopolysaccharidosis I.
- Human alpha-L-iduronidase: cDNA isolation and expression.
- Regional assignment of the structural gene for human alpha-L-iduronidase.
- Mucopolysaccharidosis type I subtypes. Presence of immunologically cross-reactive material and in vitro enhancement of the residual alpha-L-iduronidase activities.
