Abstract

BackgroundMutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated.ResultsWe generated a mutant mouse specifically lacking the fucose mutarotase (FucM) gene. The FucM knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv) of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP) in a mutant embryo relative to that of a wild-type embryo.ConclusionsThe observation that FucM-/- female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in FucM-/- mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.

Highlights

  • Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides

  • fucose mutarotase (FucM)-targeted clones were injected into C57BL/6 recipient blastocysts, and the obtained chimeras were crossed with C57BL/6 partners

  • We investigated the role of fucose mutarotase by generating mice in which the FucM gene was selectively ablated

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Summary

Introduction

Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. Fucose mutarotase (FucM) is an enzyme that is involved in the anomeric conversion of L-fucose [1] in the salvage pathway for GDP-fucose synthesis, which facilitates the incorporation of L-fucose into protein. The importance of fucosylation has been exemplified by the case of human congenital disorders of glycosylation (CDGs). CDG-IIc results from a defect in GDP-L-fucose transport into Golgi [2,3,4]. GDP-L-fucose is formed either by the de novo or salvage pathways, which in Golgi serves as a substrate for the glycosylation mediated by different fucosyltransferases.

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