Golden retrievers help identify a novel gene for a skin disorder

A skin disease, ichthyosis, presenting with similar clinical features in golden retriever dogs and humans shares a common genetic basis. The identification of the altered gene in dogs, not only identifies an eighth gene for an ichthyosis type in human called autosomal recessive congenital ichthyosis (ARCI), but also provides for the first time evidences for the involvement of its gene product in the cutaneous barrier. These findings are published online in Nature Genetics (15 January 2012).

This ichthyosis type, belonging to ARCI, results in generalized scaling of the skin and is diagnosed at birth. While the disease is rare in humans, it is very frequent in golden retriever dogs because of inbreeding and it has not been counter-selected.

Catherine André, head of the Canine Genetics team at the Institut de Génétique et Dévelopment de Rennes, and Judith Fischer, head of the Institute for Human Genetics at the University clinics of Freiburg, as well as Dr Eric Guaguere, veterinary dermatology specialist in Lommes, France, and their colleagues took advantage of the unique breeding history of dog populations to identify the genetic alteration(s) responsible for this skin disorder in golden retriever dogs. Authors identified a unique mutation in the PNPLA1 gene, perfectly segregating on a recessive transmission mode. They then analywed the corresponding human gene in a collection of affected individuals for which no molecular cause had previously been identified. They showed that six affected individuals belonging to two families carry distinct mutations both affecting the catalytic domain of the protein. Further experiments involving electron microscopy, immunolocalization by confocal microscopy and biochemistry analyses allowed to precise the role of the protein. PNPLA1 lipase is located in between the upper epidermal and the lower layers of the cornified layer, and is required for the correct keratinocyte differentiation. It belongs to a family of proteins, PNPLA1 to PNPLA5, that are key elements in the lipid metabolism of the cutaneous barrier.

The study performed in dogs was supported by CNRS and the European Commission (FP7-LUPA, GA201370), thanks to the excellent LUPA coordinators Anne-Sophie Lequarré and Marilou Ramos-Pamplona. The Canine Genetics team continues to collect blood and skin biopsies in all other canine ichthyoses in any breed.

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Dr Catherine André
Equipe Génétique du chien
Institut de Génétique et Développement de Rennes IGDR
UMR 6061 CNRS/Université de Rennes 1
2, Av. Léon Bernard
35043 Rennes cedex

Prepared by: CAndré