RETINAL DEGENERATION IN MOTOR-NEURON DEGENERATION - A MOUSE MODEL OF CEROID-LIPOFUSCINOSIS

Purpose. To evaluate the retinal degeneration of the motor neuron dege neration (mnd) mouse, and to confirm its inheritance pattern and gene location. Methods. In screening the mnd/mnd mouse for ocular disease, a retinal degeneration was found that was evaluated by serial electror etinography, histology, electron microscopy, indirect ophthalmoscopy, and genetic and linkage analysis. Results. In homozygous mnd mice, pho toreceptor and outer nuclear layers show cell loss by 5 weeks after bi rth. By 2 months, the peripheral retina is preferentially thinner than central retina, and by 6 months the entire retina is reduced in thick ness. The electroretinogram was extinguished by 6 months. Transmission electron microscopy at 3 and 6 months showed distinct cytoplasmic inc lusions characteristic of the curvilinear profiles seen in human ceroi d lipofuscinosis. Genetic analyses show that the retinal degeneration in mnd mice is inherited as a single autosomal gene with recessive exp ression, and a three-point cross placed the retinal degeneration at th e mnd locus on the proximal end of mouse chromosome 8. Crosses with ot her known strains with retinal degeneration were normal. Conclusions. The mnd mouse model is similar to the juvenile onset Spielmeyer-Vogt f orm of ceroid lipofuscinosis (Batten disease), and provides a good mod el for the retinal degeneration found in these patients.