New genotypes in Fy(a− b−) individuals: nonsense mutations (Trp to stop) in the coding sequence of either <i>FY A</i> or <i>FY B</i>

Rios, María; Chaudhuri, Asok; Mallinson, Gary; Sausais, Laima; Gomensoro-Garcia, A E; Hannon, Judith; Rosenberger, S; Poole, Joyce; Burgess, Gordon; Pogo, O; Reid, Marion E.

doi:10.1046/j.1365-2141.2000.01882.x

Cited by 59 publications

(47 citation statements)

References 21 publications

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“…For example, we studied a woman with a premature stop codon in exon 2 who was healthy and had borne 15 children. Dfy in mice, like FY in humans, is not an essential gene (24).…”

Section: Phenotypic Analysis Of Homozygous Dfymentioning

confidence: 99%

“…The human equivalent to mouse Dfy Ϫ/Ϫ is a nonsense mutation that produces a premature stop codon (UAG) in the coding sequence. The consequence of the mutation is the production of a truncated, nonfunctioning, and disposable protein in all cell types (22,24). For example, we studied a woman with a premature stop codon in exon 2 who was healthy and had borne 15 children.…”

Section: Phenotypic Analysis Of Homozygous Dfymentioning

confidence: 99%

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Deletion of the Murine Duffy Gene (Dfy) Reveals that the Duffy Receptor Is Functionally Redundant

Luo

Chaudhuri

Zbrzezna

et al. 2000

Molecular and Cellular Biology

102

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All of the antigenic determinants of the Duffy blood group system are in a glycoprotein (gp-Fy), which is encoded by a single-copy gene (FY) located on chromosome 1. gp-Fy is also produced in several cell types, including endothelial cells of capillary and postcapillary venules, the epithelial cell of kidney collecting ducts, lung alveoli, and the Purkinje cells of the cerebellum. This protein, which spans the cell membrane seven times, is a member of the superfamily of chemokine receptors and a malarial parasite receptor. The mouse Duffy gene (Dfy) homolog of human FY is also a single-copy gene, which maps in a region of conserved synteny with FY and produces a glycoprotein with 60% homology to the human protein. The mouse Duffy-like protein also binds chemokines. To study the biological role of gp-Fy, we generated a mouse strain in which Dfy was deleted. These homozygous Dfy ؊/؊ mice were indistinguishable in size, development, and health from wild-type and heterozygous littermates. We also examined components of the immune system and found no differences in lymph nodes or peripheral blood leukocyte levels between knockout and wild-type mice. The gross and histological anatomy of the thymus, spleen, lung, and brain showed no significant differences between mutants and wild-type mice. There was no indication of an overall difference between the knockout and wild-type mice in systematic neurological examinations. The only significant difference between Dfy ؊/؊ and Dfy ؉/؉ mice that we found was in neutrophil migration in peritoneal inflammations induced by lipopolysaccharide and thioglycolate. In mice homozygous for the deletion, there was less neutrophil recruitment into the peritoneal cavity and neutrophil influx in the intestines and lungs than in wild-type mice. Despite this, the susceptibility to Staphylococcus aureus infection was the same in the absence and in the presence of gp-Fy. Our results indicate that gp-Fy is functionally a redundant protein that may participate in the neutrophil migratory process.

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“…For example, we studied a woman with a premature stop codon in exon 2 who was healthy and had borne 15 children. Dfy in mice, like FY in humans, is not an essential gene (24).…”

Section: Phenotypic Analysis Of Homozygous Dfymentioning

confidence: 99%

Section: Phenotypic Analysis Of Homozygous Dfymentioning

confidence: 99%

Deletion of the Murine Duffy Gene (Dfy) Reveals that the Duffy Receptor Is Functionally Redundant

Luo

Chaudhuri

Zbrzezna

et al. 2000

Molecular and Cellular Biology

102

View full text Add to dashboard Cite

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“…In rare cases ACKR1 is also silenced in humans in all tissues, including brain, due to a premature stop codon in the ACKR1 open reading frame. No behavioral abnormalities, however, were described for these persons (25). Since such patients are rare, however, it is difficult to examine them systematically for neurologic and behavioral abnormalities, and the knockout mouse behavioral analysis was limited in scope.…”

Section: Introductionmentioning

confidence: 89%

Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

et al. 2014

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Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that induces whole-body tremor by activating Purkinje cells. Ackr1−/− mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1.

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“…This selective extinction is due to a mutation in a GATA box of the DARC promoter region [8]: the GATA transcription factor is driving DARC expression in cells from the erythrocytic lineage while other factors are operating in tissues where DARC is expressed like endothelial cells from the postcapillary venules, Purkinje cells, epithelial cells in the kidney collecting duct [9,10]. The Fy-negative phenotype has been found in Caucasian people but it is linked to deletion or point mutations in the reading frame of DARC [11].…”

Section: Introductionmentioning

confidence: 99%

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

Smolarek

Hattab

Hassanzadeh-Ghassabeh

et al. 2010

Cell. Mol. Life Sci.

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Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

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New genotypes in Fy(a− b−) individuals: nonsense mutations (Trp to stop) in the coding sequence of either FY A or FY B

Cited by 59 publications

References 21 publications

Deletion of the Murine Duffy Gene (Dfy) Reveals that the Duffy Receptor Is Functionally Redundant

Deletion of the Murine Duffy Gene (Dfy) Reveals that the Duffy Receptor Is Functionally Redundant

Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

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