Andrew P. Spicer

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We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo. Has2(-/-) embryos lack HA, exhibit severe cardiac and vascular abnormalities, and die during midgestation (E9.5-10). Heart explants from Has2(-/-) embryos lack the characteristic(More)
Three mammalian hyaluronan synthase genes, HAS1, HAS2, and HAS3, have recently been cloned. In this study, we characterized and compared the enzymatic properties of these three HAS proteins. Expression of any of these genes in COS-1 cells or rat 3Y1 fibroblasts yielded de novo formation of a hyaluronan coat. The pericellular coats formed by HAS1(More)
The last seven years have been exciting in the world of mucin biology. Molecular analyses of mucin genes and deduced protein structures have provided insight into structural features of mucins and tools with which to examine expression, secretion, and glycosylation, thereby enabling a better understanding of the role of mucins in normal physiological(More)
We recently found that low-molecular-weight hyaluronan was induced by cyclic stretch in lung fibroblasts and accumulated in lungs from animals with ventilator-induced lung injury. The low-molecular-weight hyaluronan produced by stretch increased interleukin-8 production in epithelial cells, and was accompanied by an upregulation of hyaluronan synthase-3(More)
We have used in situ hybridization to study the expression of the vertebrate hyaluronan synthase (Has) gene family members, designated Has1, Has2, and Has3, during mouse development. At embryonic day (E) 7.5, Has1 and Has2 are expressed throughout the gastrulating embryo. After E8.5, Has1 expression disappears, but Has2 continues to be strongly, albeit(More)
We describe a vertebrate hyaluronan and proteoglycan binding link protein gene family (HAPLN), consisting of four members including cartilage link protein. The encoded proteins share 45-52% overall amino acid identity. In contrast to the average sequence identity between family members, the sequence conservation between vertebrate species was very high.(More)
Hyaluronan has been implicated in biological processes such as cell adhesion, migration and proliferation. Traditionally, it was thought to be associated with the extracellular matrix, but, hyaluronan may also have unimagined roles inside the cell. Investigation of hyaluronan synthesis and degradation, the identification of new receptors and binding(More)
In the present study we have investigated the expression of mRNAs for hyaluronan synthase isoforms (HAS1, HAS2 and HAS3) in different cells in response to various stimuli. Human mesothelial cells, which synthesize large amounts of hyaluronan, express mRNAs encoding all three HAS isoforms, whereas their transformed counterparts, mesothelioma cells, which(More)
PURPOSE To deduce the function of the lens-specific cytoskeletal structure, the beaded filament, by blocking expression of the fiber cell-specific beaded filament protein CP49. METHODS The first exon of the mouse CP49 gene was deleted by using targeted genomic deletion techniques. Gene deletion was assessed through Southern blot analysis and PCR.(More)
In the past decade, there has been an explosion of interest in hyaluronan, an often misunderstood, biochemically simple, yet functionally complex carbohydrate polymer that is a resident of many extracellular matrices. Previously thought of as a passive, space-filling component of the extracellular matrix, the so-called "goo" concept, hyaluronan has risen to(More)