Neuronal ceroid lipofuscinosis type 8 (NCL8) in Alpine Dachsbracke

The neuronal ceroid lipofuscinoses (NCL)  are a group of heterogeneous inherited neurodegenerative diseases  occurring in various kinds of mammals, incl. dogs, cats and humans.  In some animals, the causal mutation leading to NCL has not been found and described yet. In connection with NCL in animal and humans, mutations have been identified in six different genes CLN 1,2,3,4,5,6 and 8 (Daly et al. 1998, Gupta et al. 2001). Each mutation in the given gene causes a unique form of NCL. The NCL occurs in several dog breed, such as Border Collie, English setter, American bulldog, Dachshund, Polish lowland sheepdog or Tibetan terrier.  The NCL of type 8 applies to Alpine Dachsbracke.

The characteristic feature of the NCL disease is excessive accumulation of waste compounds of lipid character (ceroid and lipofuscin) in the cells of the nervous system.  The presence of a high content of lipofuscin and its increasing pressure affects and destroys the nerve cells in the cortex and the cerebellum and the retina cells.

The cause of this disease in Alpine Dachshund is a mutation leading to deletion  ~ 50 kb of the telomere end of chromosome 37 that affects the CLN gene. Due to this mutation the entire CLN8 gene is deleted. Under normal conditions, the CLN8 protein helps to transport materials in and out of the cell structure called the endoplasmic reticulum and takes part in the regulation of lipid level in cells. Due to CLN8 deletion, the cells loose these functions and the mentioned lipopigments get accumulated.

The genetic tests are a reliable indicator of this disease and may help the responsible breeders to avoid production of affected puppies.

The symptoms of this disease seem to be very variable, even within one breed. The NCL usually includes neurological symptoms, such as disorientation, anxiety and aggressiveness, seizures and food intake difficulty. Sudden loss of vision is a common sign. The onset and clinical course of the disease are very variable and individual. The degree of neurodegeneration increases with the age and psychical abnormalities and spasms develop in each dog. Changes in gait – stumbling gait and limb stiffness can be observed as well. As the disease is incurable, it ends by premature death of the dog.

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Publication:
M. Hirz, M. Drögemüller, A. Schänzer, V. Jagannathan, E.Dietschi, H.H.Goebel,W.Hecht, S. Laubner, M.J. Schmidt, F. Steffen, M. Hilbe, K. Köhler, C. Drögemüller, C. Herden: Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog; Molecular Genetics and Metabolism 120 (2017) 269–277