Introduction

A novel congenital acantholytic dermatosis was recognized in Chesapeake Bay retriever dogs, which was apparent immediately after birth with superficial epidermal layers sloughing off upon pressure. At three months of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss.

Objectives

The first objective was to thoroughly characterize the disease in Chesapeake Bay retrievers and determine the cause of disease to provide a molecular test for breeders. The second objective was to provide a spontaneous animal model of this rare disease in humans.

Results

Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. Pedigree analysis was most consistent with an autosomal recessive trait. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunomapping of desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing experiments revealed a splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin.

Conclusions

The clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. These types of congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare in humans. This inbred line of dogs is the first spontaneous animal model available to study this human disease that occurs at a rate of < 1 per 1,000,000 live births.