Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation

Abstract

Hyaluronidases are endoglycosidases that initiate the breakdown of hyaluronan (HA), an abundant component of the vertebrate extracellular matrix. In humans, six paralogous genes encoding hyaluronidase-like sequences have been identified on human chromosomes 3p21.3 (HYAL2–HYAL1–HYAL3) and 7q31.3 (SPAM1–HYAL4–HYALP1). Mutations in one of these genes, HYAL1, were reported in a patient with mucopolysaccharidosis (MPS) IX. Despite the broad distribution of HA, the HYAL1-deficient patient exhibited a mild phenotype, suggesting other hyaluronidase family members contribute to constitutive HA degradation. Hyal3 knockout (Hyal3−/−) mice were generated to determine if HYAL3 had a role in constitutive HA degradation. Hyal3−/− mice were viable, fertile, and exhibited no gross phenotypic changes. X-ray analysis, histological studies of joints, whole-body weights, organ weights and the serum HA levels of Hyal3−/− mice were normal. No evidence of glycosaminoglycan accumulation, including vacuolization, was identified in the Hyal3−/− tissues analyzed. Remarkably, the only difference identified in Hyal3−/− mice was a subtle change in the alveolar structure and extracellular matrix thickness in lung-tissue sections at 12–14 months-of-age. We conclude that HYAL3 does not play a major role in constitutive HA degradation.