New cerebellar ataxia gene identified in dogs

Researchers at the University of Helsinki and the Folkhälsan Research Center have identified the genetic cause of early-onset progressive cerebellar degeneration the Finnish Hound dog breed. A mutation was identified in the SEL1L gene, which, at the same time, represents a novel candidate gene in human early-onset degenerative ataxias.

The SEL1L gene has no previous link to inherited cerebellar ataxias. The study, led by Professor Hannes Lohi, revealed a new disease mechanism, which will hopefully shed more light in to the pathogenesis of neuronal degeneration.

The amino acid change in SEL1L hits an evolutionary conserved functional domain, and is very likely to affect the normal function of the protein. SEL1L functions in quality control of newly synthesized proteins, in a cell organelle referred to as the endoplasmic reticulum. A failure in the quality control system causes endoplasmic reticulum stress and eventually cell death.

– It is very interesting that although the SEL1L gene is expressed in several different tissues, we only saw pathological changes in the cerebellar cortex of affected dogs. It is known that certain neurons in the cerebellar cortex seem to be very sensitive to endoplasmic reticulum stress, which might offer some explanation to the cerebellum-restricted cell loss, tells M.Sc Kaisa Kyöstilä, the first author of the article.

The researchers were also able to measure increased endoplasmic reticulum stress in the affected puppies’ cerebellar cortex, which gives more support to SEL1L as the causative gene in Finnish Hound ataxia.

This gene find is the first in canine early-onset cerebellar degeneration, and has enabled the development of a genetic test to help eradicate the disease from the breed. At the same time, SEL1L represents a novel candidate gene in human early-onset degenerative ataxias.

The research was published in the scientific journal PLoS Genetics on June 14, 2012.

 

Text: Päivi Lehtinen
Photo: A Finnish Hound Dog working. (The Finnish Hound Dog Association).

Press release