Disease relevance of Fbxw4

• We report here the identification and characterization of a novel dominant zebrafish mutation, hagoromo (hag), which was generated by insertional mutagenesis using a pseudotyped retrovirus [1].

High impact information on Fbxw4

• One of these, SHFM3, maps to chromosome 10q24 (Refs 6,7), which is syntenic to the Dac region on chromosome 19, and may disrupt the orthologue of Dac [2].
• 1. Amino acid sequence similarity, conserved exon-intron boundaries and conserved synteny indicated that zebrafish hag is an ortholog of mouse Dactylin, the gene mutated in the Dactylaplasia (Dac) mouse [1] [1].
• Epitope specificity of the mAb was determined by competitive binding inhibition of a given labeled mAb to solid phase fixed Dac g I or Lol p I by the mAb [3].
• Characterization of Dac g 4, a major basic allergen from Dactylis glomerata pollen [4].
• 4. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting showed that Dac g 4-related proteins of similar molecular mass were detected in the majority of allergenic grass pollen species [4].

Biological context of Fbxw4

• Comparison of the genomic organization of Fbxw6, which is located on mouse chromosome 3.3E3, with that of mouse Fbxw1, Fbxw2, and Fbxw4 showed only a low level of similarity, indicating that these genes diverged relatively early and thereafter evolved independently [5].
• On the SM/Ckc background on which the mutation occurred, Dac homozygotes die around birth [6].
• We demonstrate that the developmental mechanism underlying loss of central rays in Dac limbs is dramatic cell death of the apical ectodermal ridge, or AER [7].
• Thus, our results demonstrate that cell death of the AER in Dac limbs silences the role of the AER as key regulator of limb outgrowth, and that Fgf-8 is a strong candidate for the cause of the Dac phenotype [7].
• Partial nucleotide sequencing and inferred amino acid sequence showed greater than 90% homology with the group II allergen from Lolium perenne (Lol II) indicating they encode the group II equivalent, Dac g II [8].

Anatomical context of Fbxw4

• This cell death pattern is apparent in E10.5-11.5 Dac limb buds stained with the supravital dye Nile Blue Sulfate [7].

Co-localisations of Fbxw4

• We demonstrate that Fgf8 expression in wild type limbs colocalizes spatially and temporally with AER cell death in Dac limbs [7].

Other interactions of Fbxw4

• Mapping the mouse dactylaplasia mutation, Dac, and a gene that controls its expression, mdac [6].
• Furthermore, in our mapping panel, there is an absence of recombinants between Fgf-8 and the Dac locus in 133 backcross progeny with a median linkage estimate of approximately 0.5 cM [7].

Analytical, diagnostic and therapeutic context of Fbxw4

• Western blot immunoprobing of recombinant lysates with rabbit polyclonal, mouse monoclonal and human polyclonal antisera demonstrates immunological identity between recombinant Dac g II, Lol p I and Lol p II [8].
• Recombinant pollen allergens from Dactylis glomerata: preliminary evidence that human IgE cross-reactivity between Dac g II and Lol p I/II is increased following grass pollen immunotherapy [8].

References