The project seeks to define the inborn biochemical anomaly in the ceroidlipofuscinoses using the ovine model and to extend this knowledge to the analogous diseases of children by utilization of this knowledge and the technology developed to the study of human autopsy material. Definition of these diseases in biochemical terms opens the way to precise diagnosis and control by prenatal or heterozygote detection linked to genetic counselling services and possibly improved therapy. It particularly explores the hypothesis that these diseases are lysosomal proteinoses similar to the ovine disease. In the latter, research will be aimed at defining the pathogenic mechanisms whereby part of the lipid binding protein of mitochondrial ATPase because the dominantly stored component in the storage lipopigment. This will use ultrastructural immunocytochemical techniques to explore the anomalous distribution of this peptide within the cell, a search for a putative missing protease nd a collaborative experiment to sequence the two genes and their lead sequences that code for and direct this protein. This latter study utilizes DNA probes already developed and used to help sequence the essentially identical bovine and human genome.
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