title: RAX is required for fly neuronal development and mouse embryogenesis.
abstract: RAX was originally discovered as the unique cellular activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent findings indicate that RAX is also a critical component of the RNA-induced silencing complex and a regulator of transcription. Here we report novel phenotypes for both fruit flies carrying a transposon insertion in the 5' UTR of dRax (independently identified as loqs/R3D1) and mice with a deletion of the entire Rax gene. In Drosophila we observe a high level of dRax expression in the developing nerve cord. Mutant fly embryos homozygous for the insertion dRax[f00791] display highly abnormal commissural axon structure of the CNS and 70% of the flies homozygous for the mutant allele die prior to adulthood. Surviving male flies have reduced fertility and female flies are sterile. Furthermore, these flies appear to have a severe defect in nervous system coordination or neuromuscular function resulting in significantly reduced locomotion. Mice were also generated that are heterozygous for a deletion of the entire Rax gene (exons 1-8). While mice that are heterozygous for the mutant allele are viable and appear normal, we are unable to obtain mice homozygous for this mutant allele. Furthermore, we have not observed any embryo obtained by mating heterozygous mice at either E3.5, 7, or 14 that is nullizygous for the Rax gene. Since Rax is expressed in preimplantation blastocysts, these data indicate that deletion of the entire Rax gene is embryonic lethal in mice at a preimplantation stage of development. Collectively, these findings in two different species illustrate the importance of RAX for embryonic development.
authors.affiliation: University of Florida, Shands Cancer Center, Kevin Cameron Laboratory, 1376 Mowry Road, P.O. Box 103633, Gainesville, FL 32610-3633, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bennett
authors.forename: William L
authors.initials: WL
authors.lastname: Blalock
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Choi
authors.forename: Young J
authors.initials: YJ
authors.lastname: Lee
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: S Paul
authors.initials: SP
authors.lastname: Oh
authors.forename: W Stratford
authors.initials: WS
authors.lastname: May
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001755:Blastocyst / Q000473:pathology; D002490:Central Nervous System / Q000196:embryology*; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D020964:Embryo Loss / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005838:Genotype; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C503213:Loqs protein, Drosophila; D016601:RNA-Binding Proteins; C105441:Rax protein, mouse; D014157:Transcription Factors