OVINE NEURONAL CEROID-LIPOFUSCINOSIS - A LARGE ANIMAL-MODEL SYNTENIC WITH THE HUMAN NEURONAL CEROID-LIPOFUSCINOSIS VARIANT CLN6

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited deg enerative neurological diseases affecting children. A number of non-al lelic variants have been identified within the human population and th e genes for some of these have recently been identified. The underlyin g mechanism for the neuropathology remains an enigma; however, pioneer ing studies with the naturally occurring ovine model (OCL) have led to the proposal that these diseases represent lesions in specific hydrop hobic protein degradation pathways. In this study, we show linkage bet ween OCL and microsatellite markers on OAR 7q13-15. Using interspecies chromosome painting we establish that OAR 7q13-15 is syntenic with hu man chromosome 15q21-23, the region which was recently defined as the location of a newly identified late infantile variant (CLN6). We propo se that our ovine model represents a mutation in the gene orthologous to that mutated in the human late infantile variant CLN6. The ovine li nkage flock, consisting of 56 families, represents a powerful resource for positional cloning of this NCL gene. The availability of such a l arge animal model will have important implications for experimentation in downstream corrective therapies.