The English setter with ceroid-lipofuscinosis: a suitable model for the juvenile type of ceroid-lipofuscinosis in humans.

Genetic and histological examinations (light and EM) of tissues of an inbred line of English setters have proved that these dogs suffer a general metabolic autosomal recessive disease, canine ceroid-lipofuscinosis (CCL) almost identical to the human Stengel-Batten-Spielmeyer-Vogt disease, or neuronal ceroid-lipofuscinosis (NCL). A controlled longitudinal morphologic study showed that the formation and accumulation of an autofluorescent lipopigment, identified as "ceroid" in the isolated state, appears in the neurons already in 2-day-old puppies and increases linearly with time. Clinical signs and symptoms develop after a distinct loss of neurocytoplasm and its functional organelles is demonstrable. At that time, loss of functional neuronal cytoplasm appears to result from pigment formation. Nerve cells which have suffered this fate will eventually die and disappear. The process leads to severe global neurologic disturbance and cerebral atrophy. By the time of death from the disease at age 20 to 27 months, brain weight is reduced to 60-70% of normal control animals. The English setter with CCL differs somewhat from humans in the degree of morphological damage to various layers of the retina. In human with NCL, there is a pronounced loss of photoreceptors in the end-stage of the disease, but in CCL only minimal structural damage is observed in the retina. For experimental treatment protocols for NCL, the CCL setter is a useful model.