Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure.

Background: Hyaluronan (HA) is required for endothelial-to-mesenchymal transition and normal heart development in the mouse. Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient ( ) mice and humans suggested removal of HA is also important for normal heart development. We have performed longitudinal studies of heart structure and function in mice to determine when, and how, HYAL2 deficiency leads to these abnormalities.

Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism.

Hyaluronidase 2 (HYAL2) is a membrane-anchored protein that is proposed to initiate the degradation of hyaluronan (HA) in the extracellular matrix. The distribution of HYAL2 in tissues, and of HA in tissues lacking HYAL2, is largely unexplored despite the importance of HA metabolism in several disease processes. Herein, we use immunoblot and histochemical analyses to detect HYAL2 and HA in mouse tissues, as well as agarose gel electrophoresis to examine the size of HA.

Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression.

Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G, p.

Long-term correction of Sandhoff disease following intravenous delivery of rAAV9 to mouse neonates.

G(M2) gangliosidoses are severe neurodegenerative disorders resulting from a deficiency in β-hexosaminidase A activity and lacking effective therapies. Using a Sandhoff disease (SD) mouse model (Hexb(-/-)) of the G(M2) gangliosidoses, we tested the potential of systemically delivered adeno-associated virus 9 (AAV9) expressing Hexb cDNA to correct the neurological phenotype. Neonatal or adult SD and normal mice were intravenously injected with AAV9-HexB or -LacZ and monitored for serum β-hexosaminidase activity, motor function, and survival.

Mutation of EMG1 causing Bowen-Conradi syndrome results in reduced cell proliferation rates concomitant with G2/M arrest and 18S rRNA processing delay.

Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive disorder caused by a D86G substitution in the protein, Essential for Mitotic Growth 1 (EMG1). EMG1 is essential for 18S rRNA maturation and 40S ribosome biogenesis in yeast, but no studies of its role in ribosome biogenesis have been done in mammals. To assess the effect of the EMG1 mutation on cell growth and ribosomal biogenesis in humans, we employed BCS patient cells.

Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction.

Hyaluronidase (HYAL) 2 is a membrane-anchored protein that is proposed to hydrolyze hyaluronan (HA) to smaller fragments that are internalized for breakdown. Initial studies of a Hyal2 knock-out (KO) mouse revealed a mild phenotype with high serum HA, supporting a role for HYAL2 in HA breakdown. We now describe a severe cardiac phenotype, deemed acute, in 54% of Hyal2 KO mice on an outbred background; Hyal2 KO mice without the severe cardiac phenotype were designated non-acute.

Hyaluronidase 1 and β-hexosaminidase have redundant functions in hyaluronan and chondroitin sulfate degradation.

Hyaluronan (HA), a member of the glycosaminoglycan (GAG) family, is a critical component of the extracellular matrix. A model for HA degradation that invokes the activity of both hyaluronidases and exoglycosidases has been advanced. However, no in vivo studies have been done to determine the extent to which these enzymes contribute to HA breakdown.

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

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.

A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis.

Hyaluronidases are endoglycosidases that hydrolyze hyaluronan (HA), an abundant component of the extracellular matrix of vertebrate connective tissues. Six human hyaluronidase-related genes have been identified to date. Mutations in one of these genes cause a deficiency of hyaluronidase 1 (HYAL1) resulting in a lysosomal storage disorder, mucopolysaccharidosis (MPS) IX.

Mouse Hyal3 encodes a 45- to 56-kDa glycoprotein whose overexpression increases hyaluronidase 1 activity in cultured cells.

Hyaluronidases are enzymes that mediate the breakdown of hyaluronan (HA), a large polysaccharide abundant in the extracellular matrix of vertebrate tissues. Six genes have been predicted to encode hyaluronidases in humans, but the protein products of only SPAM1, HYAL1, and HYAL2 have been characterized. We have now expressed the mouse Hyal3 gene product, hyaluronidase 3 (Hyal3), in Baby Hamster Kidney (BHK) cells and demonstrated the presence of multiple forms of Hyal3 ranging from approximately 45 to 56 kDa in expression lysates.