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WormBase Tree Display for Variation: WBVar00250006

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Name Class

WBVar00250006NamePublic_nametm985
HGVSgCHROMOSOME_I:g.11701583_11701929del
Sequence_detailsSMapS_parentSequenceT22H2
Flanking_sequencesgtcggaagccggcgaaaattgtcagaagcttaattttagaaatttttagaaattaaattt
Mapping_targetT22H2
Source_location7CHROMOSOME_I1170158211701930Inferred_automaticallyNational_Bioresource_Project
Type_of_mutationDeletion
PCR_producttm985_external
tm985_internal
SeqStatusSequenced
Variation_typeAllele
OriginSpeciesCaenorhabditis elegans
Component_of_genotype (14)
LaboratoryFX
AuthorMitani S
DB_infoDatabaseNational_Bioresource_Projectseq985
NBP_allele
StatusLive
AffectsGeneWBGene00011936
TranscriptT22H2.6b.1VEP_consequencesplice_donor_variant,coding_sequence_variant,5_prime_UTR_variant,intron_variant
VEP_impactHIGH
Intron_number1/4
Exon_number1/5
T22H2.6a.1VEP_consequencesplice_donor_variant,coding_sequence_variant,5_prime_UTR_variant,intron_variant
VEP_impactHIGH
Intron_number2/5
Exon_number1-2/6
IsolationMutagenTMP/UV
GeneticsMapI
DescriptionPhenotypeWBPhenotype:0000154Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkThe homozygous mutant had approximately 20% reduction in total number of progeny (Fig. S4C).Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBPhenotype:0000473Paper_evidenceWBPaper00061552
Curator_confirmedWBPerson712
Remarkanimals display adult onset paralysisPaper_evidenceWBPaper00061552
Curator_confirmedWBPerson712
Rescued_by_transgeneWBTransgene00026278
EQ_annotationsLife_stageWBls:0000041PATO:0000460Paper_evidenceWBPaper00061552
Curator_confirmedWBPerson712
WBPhenotype:0000885Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkTime to clearance is decreased. We used four-dimensional Nomarski time lapse video microscopy to follow the first 13 programmed cell deaths in the AB cell lineage (32). By using this technique, we found striking alterations in the kinetics of cell death (Fig. 3). The time from which initial morphological signs of apoptosis are seen until the time at which the dying cell is completely eliminated and disappears is referred to as the time to clearance (Fig. 3A). We observed a striking change in the mean time to clearance, which was decreased by nearly half in pgrn-1 mutants (harmonic mean of 5.7 min in pgrn-1 mutants vs. 10.7 min in WT; P < 0.0036; Fig. 3B and Table S4) This indicates that, when the cell death program has been initiated, corpse clearance is accelerated in pgrn-1 mutants.Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0004015PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
Life_stageWBls:0000003PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBPhenotype:0002045Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkWe counted apoptotic corpses in embryos at several developmental stages and found significantly fewer apoptotic bodies in pgrn-1 mutants compared with control animals(Fig. 2A). To verify that the cell death defect was a result of progranulin deficiency, we reintroduced the C. elegans progranulin gene and observed partial rescue of the mutant phenotype (Fig. S4D). We speculate that the incomplete rescue maybe because expression of pgrn-1 from a transgene does not fully mimic the expression of the endogenous gene. In addition to cell deaths that occur as part of the developmental program, apoptosis can be triggered in the germ line by UV irradiation. We found that pgrn-1 mutations did not affect UV-induced germ cell death(Fig. 2B).Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
EQ_annotationsLife_stageWBls:0000003PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
Phenotype_not_observedWBPhenotype:0000039Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkHomozygous and heterozygous mutants exhibited a normal lifespan (Fig. S4B and Tables S1 and S2). Likewise, overexpression of progranulin did not significantly alter lifespan (Fig. S4B and Table S3).Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBPhenotype:0000062Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
RemarkClassified as homozygous viable by the National Bioresource Project of Japan.Person_evidenceWBPerson7743
Curator_confirmedWBPerson712
WBPhenotype:0000100Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkWe found that pgrn-1 mutations did not affect UV-induced germ cell death(Fig. 2B).Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0006796PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBPhenotype:0000520Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkThe pgrn-1(tm985) allele contains a 347-bp deletion encompassing part of the progranulin promoter, all of exon 1, and part of the first intron (Fig. S1). Animals carrying this mutation did notproduce progranulin mRNA as assayed by quantitative RT- PCR(Fig. S4A). Thus, pgrn-1(tm985)is likely to be a null allele. pgrn-1 mutants appeared grossly normal.Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBPhenotype:0001172Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
RemarkThe same number of ODR-1::RFP fluorescent cell bodies were observed in pgrn-1 mutants and controls, suggesting that cell death occurs normally in the I1 and ASI lineage (Fig. 2C). We also used a LIN-11::GFP reporter which is seen in approximately five extra ventral cord motor neurons in strong ced-3(lf) mutants (30). Once again, pgrn-1 mutants had similar numbers of LIN-11::GFP fluorescent cell bodies compared with controls (Fig. 2D). Finally, we looked for extra cells in the anterior pharynx, where, in strong ced-3(lf) mutants, approximately 12 extra cells are found (31). Once again, pgrn-1 mutants had the same number of cells in the anterior pharynx as control worms (Fig. 2E). Taken together, our inability to find extra cells suggests that cells that normally die still do so in pgrn-1 mutants.Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
We also measured the time to die in WT and pgrn-1 mutant animals. In WT animals, the time to die for apoptotic cells is distributed in a Gaussian manner. In pgrn-1 mutants, the distribution was skewed and no longer Gaussian (P < 0.0001). However, the mean time to die of the two strains was not significantly different (harmonic mean: control, 20.2 min vs. pgrn-1 mutants, 21.7 min; Fig. 3 C and D and Table S4).Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0005116PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBbt:0005666PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBbt:0005829PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
WBbt:0003681PATO:0000460Paper_evidenceWBPaper00038205
Curator_confirmedWBPerson712
Disease_infoModels_diseaseDOID:9255
Modifies_diseaseDOID:332
Models_disease_in_annotationWBDOannot00000006
WBDOannot00001271
WBDOannot00001272
WBDOannot00001273
WBDOannot00001274
WBDOannot00001275
Modifies_disease_in_annotationWBDOannot00001023
WBDOannot00001024
WBDOannot00001035
WBDOannot00001038
WBDOannot00001041
ReferenceWBPaper00047019
WBPaper00038205
WBPaper00061552
Remark13245/13246-13592/13593 (347 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