Hereditary cutaneous mucinosis in shar pei dogs is associated with increased hyaluronan synthase-2 mRNA transcription by cultured dermal fibroblasts

Shar pei dogs are known for the distinctive feature of thick, wrinkled skin as a consequence of high dermal mucin content. Excessive dermal deposition of mucinous substance leading to severe skin folding, and/or to the more severe vesicular form characterized by dermal vesicles or bullae, is highly prevalent in this breed and is known as idiopathic mucinosis. Hyaluronic acid (HA) is the main component that accumulates in the dermis, and high levels of HA have also been detected in the serum of shar pei dogs. In this study, the cellular and molecular mechanisms underlying cutaneous mucinosis of shar pei dogs were investigated. Thirteen shar pei dogs and four control dogs of other breeds were included. In primary dermal fibroblast cultures, transcription of the family of hyaluronan synthases (HAS) involved in HA synthesis, and of hyaluronidases (HYAL) involved in HA degradation, were studied by reverse transcriptase polymerase chain reaction. The location of HA in cell cultures was studied by immunofluorescence and confocal laser microscopy. Dermal fibroblasts transcribed HAS2, HAS3, HYAL1 and HYAL2, but no amplification for HAS1 was found. A higher transcription of HAS2 was demonstrated in shar pei dogs compared with control dogs. By confocal microscopy, HA was detected as a more diffuse and intense network‐like pattern of green fluorescence in the fibroblast cells of shar pei dogs in comparison with control dogs. Together, these results provide additional evidence that hereditary cutaneous mucinosis in shar pei dogs may be a consequence of over‐transcription or increased activity of HAS2. Résumé Les Shar‐peïs sont connus pour leur peau épaisse et plissée résultant d’un taux élevé de mucine dermique. Un dépôt dermique excessif de mucine entraîne une accentuation des plis de la peau et/ou la formation d’une forme vésiculeuse sévère caractérisée par des vésicules ou bulles dermiques, connue sous le nom de mucinose idiopathique, de prévalence élevée dans cette espèce. L’acide hyaluronique (HA) est le principal composant qui s’accumule dans le derme, et des taux élevés d’HA ont aussi été détecté dans le serum des Shar‐peïs. Dans cet essai, les mécanismes cellulaires et moléculaires sous‐jacents de la mucinose des Shar‐peïs ont étéétudiés. Treize Shar‐peïs et quatre chiens contrôles d’autres races ont été inclus. Dans les cultures dermiques primaires de fibroblastes, la transcription de la famille des hyaluronan‐synthases (HAS) impliquées dans la synthèse de l’H