Biomedical subjects

Daniel J Becker

Publications and source records attributed to Daniel J Becker.

4 recordsLinked to original sources

PubMed2004

Biliary atresia associated with hypoplastic left heart syndrome: a case report and review of the literature.

Biliary atresia is a cholestatic disorder of infancy that is associated with other anatomic anomalies in approximately 20% of cases. These frequently are defects in situs determination and laterality, causing syndromes of heterotaxy and complex heart defects. The authors describe an infant with both biliary atresia and hypoplastic left heart syndrome (HLHS) in the absence of a laterality defect or evidence of any other morphologic defect. The presence of a hypoplastic left ventricle in a patient with biliary atresia has previously been reported only in the context of a heterotaxy syndrome. The coexistence of these 2 disorders raises etiologic considerations and represents a potential challenge for the surgical treatment of both conditions.

Abnormalities, Multiple↗

PubMed2003

Fucose: biosynthesis and biological function in mammals.

Fucose is a deoxyhexose that is present in a wide variety of organisms. In mammals, fucose-containing glycans have important roles in blood transfusion reactions, selectin-mediated leukocyte-endothelial adhesion, host-microbe interactions, and numerous ontogenic events, including signaling events by the Notch receptor family. Alterations in the expression of fucosylated oligosaccharides have also been observed in several pathological processes, including cancer and atherosclerosis. Fucose deficiency is accompanied by a complex set of phenotypes both in humans with leukocyte adhesion deficiency type II (LAD II; also known as congenital disorder of glycosylation type IIc) and in a recently generated strain of mice with a conditional defect in fucosylated glycan expression. Fucosylated glycans are constructed by fucosyltransferases, which require the substrate GDP-fucose. Two pathways for the synthesis of GDP-fucose operate in mammalian cells, the GDP-mannose-dependent de novo pathway and the free fucose-dependent salvage pathway. In this review, we focus on the biological functions of mammalian fucosylated glycans and the biosynthetic processes leading to formation of the fucosylated glycan precursor GDP-fucose.

Animals↗

PubMed2003

Strain-specific modification of lethality in fucose-deficient mice.

The FX locus encodes an essential enzyme in the de novo pathway of GDP-fucose biosynthesis. Mice homozygous for a targeted mutation of the FX gene manifest a host of pleiotropic abnormalities including a lethal phenotype that is almost completely penetrant in heterozygous intercrosses on a mixed genetic background. Here we have investigated genetic suppression of FX-mediated lethality. Reduced recovery of heterozygous mice was observed while backcrossing the null FX allele to C57BL/6J (B6), but was less dramatic in an outcross to CASA/Rk and absent in an outcross to 129S1/SvImJ, indicating that genetic background modifies survival of FX+/- progeny. Substantial strain-specific differences in pre- and postnatal survival of FX-/- progeny were also detected in heterozygous crosses of C57BL/6J congenic, 129S1B6F1, and B6CASAF1 mice. Specifically, intrauterine survival of FX-/- mice was greatly increased during a heterozygous intercross on a uniform C57BL/6J genetic background compared with survival on a hybrid genetic background consisting of a mixture of C57BL/6J and 129S2/SvPas. In addition, statistically significant clustering of FX-/- progeny into litters and specific breeding cages was noted during a B6CASAF1 FX+/- intercross, suggesting a rare mechanism for modifier gene action in which parentally expressed genes define the phenotype, in this case the survival potential, of mutant offspring. Our results disclose that lethality in FX mutant mice is determined by one or more strain-specific modifier loci.

Alleles↗

PubMed2002

Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus.

Glycoprotein fucosylation enables fringe-dependent modulation of signal transduction by Notch transmembrane receptors, contributes to selectin-dependent leukocyte trafficking, and is faulty in leukocyte adhesion deficiency (LAD) type II, also known as congenital disorder of glycosylation (CDG)-IIc, a rare human disorder characterized by psychomotor defects, developmental abnormalities, and leukocyte adhesion defects. We report here that mice with an induced null mutation in the FX locus, which encodes an enzyme in the de novo pathway for GDP-fucose synthesis, exhibit a virtually complete deficiency of cellular fucosylation, and variable frequency of intrauterine demise determined by parental FX genotype. Live-born FX(-/-) mice exhibit postnatal failure to thrive that is suppressed with a fucose-supplemented diet. FX(-/-) adults suffer from an extreme neutrophilia, myeloproliferation, and absence of leukocyte selectin ligand expression reminiscent of LAD-II/CDG-IIc. Contingent restoration of leukocyte and endothelial selectin ligand expression, general cellular fucosylation, and normal postnatal physiology is achieved by modulating dietary fucose to supply a salvage pathway for GDP-fucose synthesis. Conditional control of fucosylation in FX(-/-) mice identifies cellular fucosylation events as essential concomitants to fertility, early growth and development, and leukocyte adhesion.

Animals↗