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PMID:18634873

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Citation

Bennett, RL, Blalock, WL, Choi, EJ, Lee, YJ, Zhang, Y, Zhou, L, Oh, SP and May, WS RAX is required for fly neuronal development and mouse embryogenesis. Mech. Dev. 125:777-85

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.

Links

PubMed PMC2562589 Online version:10.1016/j.mod.2008.06.009

Keywords

Amino Acid Sequence; Animals; Blastocyst/pathology; Central Nervous System/embryology; Crosses, Genetic; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/embryology; Drosophila melanogaster/genetics; Embryo Loss/metabolism; Embryo, Nonmammalian/metabolism; Embryonic Development; Eye Proteins/chemistry; Eye Proteins/genetics; Eye Proteins/metabolism; Female; Gene Deletion; Gene Expression Regulation, Developmental; Gene Targeting; Genotype; Homeodomain Proteins/chemistry; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Male; Mice; Molecular Sequence Data; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Recombination, Genetic/genetics; Sequence Homology, Amino Acid; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:M9MRT5

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q27IS6

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q27IS7

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q4TZM6

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IP72

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VJY9

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:X2J5X6

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:X2JAB1

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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