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WormBase Tree Display for Variation: WBVar00249869

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Name Class

WBVar00249869NamePublic_nametm843
Other_nameC30H6.6.1:c.487+12_1146del
HGVSgCHROMOSOME_IV:g.17377430_17378268del
Sequence_detailsSMapS_parentSequenceC30H6
Flanking_sequencestactgcttgcaaattgcaggcaagttgtgaggagcttcatctaggcttctcgagctgaaa
Mapping_targetC30H6
Source_location7CHROMOSOME_IV1737742917378269Inferred_automaticallyNational_Bioresource_Project
Type_of_mutationDeletion
PCR_producttm843_external
tm843_internal
SeqStatusSequenced
Variation_typeAllele
OriginSpeciesCaenorhabditis elegans
LaboratoryFX
AuthorMitani S
DB_infoDatabaseNational_Bioresource_Projectseq843
NBP_allele
StatusLive
AffectsGeneWBGene00001811
TranscriptC30H6.6.1VEP_consequencesplice_acceptor_variant,splice_donor_variant,coding_sequence_variant,intron_variant
VEP_impactHIGH
HGVScC30H6.6.1:c.487+12_1146del
cDNA_position?-1155
CDS_position?-1146
Protein_position?-382
Intron_number4-7/10
Exon_number5-8/11
Interactor (16)
IsolationMutagenTMP/UV
GeneticsMapIV
DescriptionPhenotypeWBPhenotype:0000031Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Remark"Apart from a slightly impaired growth rate, haf-1 mutants are indistinguishable from WT worms under normal laboratory conditions. However, development of haf-1 mutants was delayed when mitochondrial protein folding was perturbed either by spg-7(RNAi) or by hsp-60(RNAi), whereas conditions that perturb ER protein folding had no deleterious effects on development of haf-1 mutants (Figure 2A)."Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0034514PATO:0000460Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Phenotype_assayGenotypespg-7(RNAi) or hsp-60(RNAi)Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
WBPhenotype:0000137Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Remark"In two models of mitochondrial stress, feeding of spg-7(RNAi) as well as a previously characterized temperature-sensitive allele (zc32) (Benedetti et al., 2006), GFP fluorescence increased over the course of postembryonic development. The increase in fluorescence and GFP levels was attenuated in haf-1(ok705) deletion animals (Figures 1A and 1B). Inhibition of the UPRmt reporter was mirrored by the effects of haf-1(ok705) and haf-1(tm843) deletions on the expression of the endogenous mitochondrial chaperone gene hsp-60, as determined by quantitative RT-PCR (Figure 1C)."Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
"In two models of mitochondrial stress, feeding of spg-7(RNAi) as well as a previously characterized temperature-sensitive allele (zc32) (Benedetti et al., 2006), GFP fluorescence increased over the course of postembryonic development. The increase in fluorescence and GFP levels was attenuated in haf-1(ok705) deletion animals (Figures 1A and 1B). Inhibition of the UPRmt reporter was mirrored by the effects of haf-1(ok705) and haf-1(tm843) deletions on the expression of the endogenous mitochondrial chaperone gene hsp-60, as determined by quantitative RT-PCR (Figure 1C). Similar results were obtained for the mitochondrial HSP70 gene, hsp-6 (Figures S1C and S1D)."Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0034514PATO:0000460Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Phenotype_assayGenotypehsp-6(RNAi) or spg-7(RNAi)Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
WBPhenotype:0000145Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Remark"Both haf-1 mutants strongly suppressed the infertility phenotype of ub-m-nonN-Nmnat1 (Figure 3e and Supplementary Table S2)."Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotypegcIs40 [ub-m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
WBPhenotype:0001090Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Remark"Compared with WT, haf-1-deleted worms displayed markedly impaired survival at the elevated temperature of 30°C (Figure S2A)."Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0010286PATO:0000460Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Phenotype_assayTemperature30Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
WBPhenotype:0001278Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Remark"Consistent with this hypothesis, basal mitoUPR induction by m-nonN-Nmnat1 was significantly suppressed by haf-1(lf) (Figure 4e)."Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotypezcIs13 [Phsp-6::GFP]; gcIs41 [Neuro-m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
WBPhenotype:0001918Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Remark"However, taxol was lethally toxic to elderly haf-1 but not atfs-1 loss-of-function animals (Figure 5d)."Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00003010Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotypezdIs5 [Pmec-4::GFP; lin-15AB(+)]; gcIs35 [Prab3::mCherry::m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
WBPhenotype:0002423Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Remark"However, we found that loss-of-function mutations in the gene haf-1, which encodes a mitochondrial outer membrane ABC transporter previously shown to function as an activator of the mitochondrial unfolded protein response (mitoUPR), significantly suppressed the hypoxia resistance of both ub-m-nonN-Nmnat1 and neuro-m-nonN-Nmnat1 transgenes (Figures 3a and b)."Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0001666PATO:0000460Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotypegcIs40 [ub-m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
gcIs30 [Neuro-m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_not_observedWBPhenotype:0000039Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Remark"However, surprisingly, haf-1(tm843) did not suppress lifespan extension (Figure 3f)." of ub-m-nonN-Nmnat1 (also Supplementary Table S2)Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
haf-1(tm843) did not significantly affect lifespan extension (Figure 3f, Supplementary Table S2)Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotypegcIs40 [ub-m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
WBPhenotype:0000062Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
RemarkClassified as homozygous viable by the National Bioresource Project of Japan.Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
Laboratory_evidenceFX
WBPhenotype:0000523Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Remark"By contrast, haf-1-deleted worms were indistinguishable from WT in their survival under reductive stress imposed by dithiothreitol (DTT), which promotes ER stress and activates the UPRER (Figure S2B)."Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004908Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0042221PATO:0000460Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Phenotype_assayTreatmentAnimals were exposed to 5 millimolar dithiothreitol (DTT) and assayed for survival over several daysPaper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
WBPhenotype:0000743Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
RemarkComments to the National Bioresource Project of Japan: Dr. L. Timmons: negative for RNAi defects using various feeding strains to deliver dsRNA.Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
Comment to the National Bioresource Project of Japan from Dr. L. Timmons: negative for RNAi defects using various feeding strains to deliver dsRNA.Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
Laboratory_evidenceFX
WBPhenotype:0000886Person_evidenceWBPerson7001
Curator_confirmedWBPerson712
WBPhenotype:0001258Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
Remark"Whereas the positive control, eri-1(mg366), markedly sensitized worms to dpy-13(RNAi), haf-1 deletion had no effect on the sensitivity of worms to the RNAi feeding procedure (Figure S1E)."Paper_evidenceWBPaper00035985
Curator_confirmedWBPerson2987
WBPhenotype:0002423Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
RemarkFigure 3a, 3bPaper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
"Additionally, the suppression by the haf-1 is specific to Nmnat1 hypoxia resistance in that haf-1(lf) did not suppress the hypoxic protection produced by a previously identified hypoxia-resistant allele of the arginyl tRNA synthetase gene - rars-1(gc47) (Figure 3d)."Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0001666PATO:0000460Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotyperars-1(gc47)Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
ReferenceWBPaper00035985
WBPaper00049307
Remark25783/25784-26622/26623 (839 bp deletion)
This knockout was generated by the National Bioresource Project, Tokyo, Japan, which is part of the International C. elegans Gene Knockout Consortium, which should be acknowledged in any publications resulting from its use.Paper_evidenceWBPaper00041807
MethodNBP_knockout_allele