Expression Cloning and Characterization of a Novel Murine α1,3-Fucosyltransferase, mFuc-TIX, That Synthesizes the Lewis x (CD15) Epitope in Brain and Kidney

Kudo, Takashi; Ikehara, Yuzuru; Togayachi, Akira; Kaneko, Mika K.; Hiraga, Tsuneo; Sasaki, Keisuke; Narimatsu, Hisashi

doi:10.1074/jbc.273.41.26729

Cited by 101 publications

(88 citation statements)

References 59 publications

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“…2C to F), consistent with diminished expression of mFuc-TIX (CD15 synthase) and uromodulin (uromucoid, Tamm-Horsfall glycoprotein), which are proximal and distal tubule-specific markers, respectively ( Fig. 3A and C) (25,35,48). To test the hypothesis that this tubular dysgenesis was caused by apoptotic tubular epithelial cell death, we carried out TUNEL assays to detect fragmented nuclear DNA in the kidneys of heterozygous and homozygous mutant neonatal mice.…”

Section: Resultsmentioning

confidence: 81%

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Moriguchi

Hamada

Morito

et al. 2006

Molecular and Cellular Biology

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MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains. Although it is well known that MafB is specifically expressed in glomerular epithelial cells (podocytes) and macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions in the kidney and in macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. mafB homozygous mutants displayed renal dysgenesis with abnormal podocyte differentiation as well as tubular apoptosis. Interestingly, these kidney phenotypes were associated with diminished expression of several kidney disease-related genes. In hematopoietic cells, GFP fluorescence was observed in both Mac-1-and F4/80-expressing macrophages in the fetal liver. Interestingly, F4/80 expression in macrophages was suppressed in the homozygous mutant, although development of the Mac-1-positive macrophage population was unaffected. In primary cultures of fetal liver hematopoietic cells, MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages, whereas the Mac-1-positive macrophage population developed normally. These results demonstrate that MafB is essential for podocyte differentiation, renal tubule survival, and F4/80 maturation in a distinct subpopulation of nonadherent mature macrophages.

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Section: Resultsmentioning

confidence: 81%

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Moriguchi

Hamada

Morito

et al. 2006

Molecular and Cellular Biology

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191

248

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“…Based on the sequences of mouse and human FucT-IX genes (44,49), oligonucleotides used to amplify the cDNA were as follows: 5Ј-ATGACATCAACATCCAAAGGCATT-3Ј and 5Ј-ACCAA-CAGACTTATATTCTTGATGCC-3Ј. The PCR product was subcloned into the pBluescript SKϪ, and the subcloned fragments were sequenced.…”

Section: Methodsmentioning

confidence: 99%

“…Each member of the ␣3FucT family differs in its ability to synthesize Lewis x and/or sialyl Lewis x epitopes. While FucT-III, -V, and -VI synthesize both epitopes (39,40), FucT-VII synthesizes only sialyl Lewis x (42,43,48), and FucT-IV and -IX synthesize Lewis x but little or no sialyl Lewis x (37,44,49).…”

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confidence: 99%

Pax6 Controls the Expression of Lewis x Epitope in the Embryonic Forebrain by Regulating α1,3-Fucosyltransferase IX Expression

Shimoda¹,

Tajima²,

Osanai³

et al. 2002

Journal of Biological Chemistry

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Pax6 is a transcription factor involved in brain patterning and neurogenesis. Expression of Pax6 is specifically observed in the developing cerebral cortex, where Lewis x epitope that is thought to play important roles in cell interactions is colocalized. Here we examined whether Pax6 regulates localization of Lewis x using Pax6 mutant rat embryos. The Lewis x epitope disappeared in the Pax6 mutant cortex, and activity of ␣1,3-fucosyltransferase, which catalyzed the last step of Lewis x biosynthesis, drastically decreased in the mutant cortex as compared with the wild type. Furthermore, expression of a fucosyltransferase gene, FucT-IX, specifically decreased in the mutant, while no change was seen for expression of another fucosyltransferase gene, FucT-IV. These results strongly suggest that Pax6 controls Lewis x expression in the embryonic brain by regulating FucT-IX gene expression.

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“…Fuc-TIX is mainly involved in Le x biosynthesis and has not been shown to contribute to selectin ligand biosynthesis (22)(23)(24).…”

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confidence: 99%

Polymorphonuclear Leukocytes from Individuals Carrying the G329A Mutation in the α1,3-Fucosyltransferase VII Gene (FUT7) Roll on E- and P-Selectins

Bengtson

Lundblad

Larson

et al. 2002

The Journal of Immunology

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We recently identified several individuals carrying a missense mutation (G329A; Arg110-Gln) in the FUT7 gene encoding fucosyltransferase VII. This enzyme is involved in the biosynthesis of the sialyl Lewis x (Lex) epitope on human leukocytes, which has been identified as an important component of leukocyte ligands for E- and P-selectin. No enzyme activity was measurable in expression studies in COS-7 cells using the mutated FUT7 construct. One of the identified individuals carried this mutation homozygously. Flow cytometry analysis of polymorphonuclear leukocytes (PMN) from this individual showed a nearly complete absence of staining with mAbs directed against sialyl Lex and a diminished staining with an E-selectin IgG chimera. However, staining with P-selectin IgG chimera and Abs directed against P-selectin glycoprotein ligand-1 was not affected by the mutation. PMN from the homozygously mutated individual was further analyzed in an in vitro flow chamber assay. The number of rolling PMN and the rolling velocities on both E- and P-selectin were in the range of PMN from nonmutated individuals. FUT4 and FUT7 mRNA was quantified in PMN isolated from individuals carrying the FUT7 mutation. It was found that PMN from both FUT7 homozygously and heterozygously mutated individuals exhibited an elevated expression of FUT4 mRNA compared with PMN from FUT7 nonmutated individuals. The elevated expression of fucosyltransferase IV was reflected as an increased expression of the Lex and CD65s Ags on PMN from these individuals. The significance of the mutation was supported by transfection of BJAB cells.

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Expression Cloning and Characterization of a Novel Murine α1,3-Fucosyltransferase, mFuc-TIX, That Synthesizes the Lewis x (CD15) Epitope in Brain and Kidney

Cited by 101 publications

References 59 publications

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Pax6 Controls the Expression of Lewis x Epitope in the Embryonic Forebrain by Regulating α1,3-Fucosyltransferase IX Expression

Polymorphonuclear Leukocytes from Individuals Carrying the G329A Mutation in the α1,3-Fucosyltransferase VII Gene (FUT7) Roll on E- and P-Selectins

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