Ichthyosis is a broad term for a group of hereditary skin disorders with various presentations, usually including scaling of the skin. Some forms are relatively mild, whereas others are quite severe. Previous research has identified several genes and gene regions that are associated with some forms of ichthyosis, but for other forms, the underlying genetic causes are not known. For rare diseases, determining the genetic causes can be challenging, in part because so few people are affected by them that researchers cannot obtain sufficient examples.

Animal models can be useful both for identifying causative mechanisms for disorders that aren't understood and for evaluating treatment options for disorders whose bases are known. For example, mutations in two genes (KRT10 and TGM1) are associated with forms of ichthyosis in both humans and dog breeds (Norfolk terrier and Jack Russell terrier, respectively). Because each dog breed has a high degree of homogeneity, they are promising models for studies of genetically linked diseases such as ichthyosis.

In 2007, a spontaneous ichthyosis resembling some forms of human ichthyosis was described in golden retriever dogs. Recently, a group of European researchers directed by Catherine André (Centre National de la Recherche Scientifique and Université Rennes 1, Rennes, France) and Judith Fischer (Centre National de Génotypage, Evry, France and Institute for Human Genetics and Universität Freiburg, Freiburg, Germany) carried out a genetic association study in 40 golden retrievers to look for potential causes of this ichthyosis. The team found that the ichthyosis in these dogs was caused by mutations in the gene PNPLA1. Furthermore, mutations in the human version of the gene were found in six individuals from two families with ichthyosis for which previous studies had failed to identify a cause (Nat. Genet. 44, 140–147; 2012).

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The protein encoded by PNPLA1 belongs to a family of phospholipases, enzymes that break down fats, including those that form cell membranes. In skin samples from golden retrievers and one person with ichthyosis and PNPLA1 mutations, membranes of cells in the epidermal skin layer were abnormal. PNPLA1 was not previously known to be associated with ichthyosis or other diseases; the discovery of its involvement provides a new link between the PNPLA gene family and ichthyosis.

Forms of ichthyosis occur in several other dog breeds, and these study results offer hope that similar genetic association studies in those breeds may help to identify other genes involved in human ichthyosis.