WormBase Tree Display for Variation: WBVar00250006
expand all nodes | collapse all nodes | view schema
WBVar00250006 | Name | Public_name | tm985 | ||||||
---|---|---|---|---|---|---|---|---|---|
HGVSg | CHROMOSOME_I:g.11701583_11701929del | ||||||||
Sequence_details | SMap | S_parent | Sequence | T22H2 | |||||
Flanking_sequences | gtcggaagccggcgaaaattgtcagaagct | taattttagaaatttttagaaattaaattt | |||||||
Mapping_target | T22H2 | ||||||||
Source_location | 7 | CHROMOSOME_I | 11701582 | 11701930 | Inferred_automatically | National_Bioresource_Project | |||
Type_of_mutation | Deletion | ||||||||
PCR_product | tm985_external | ||||||||
tm985_internal | |||||||||
SeqStatus | Sequenced | ||||||||
Variation_type | Allele | ||||||||
Origin | Species | Caenorhabditis elegans | |||||||
Component_of_genotype (14) | |||||||||
Laboratory | FX | ||||||||
Author | Mitani S | ||||||||
DB_info | Database | National_Bioresource_Project | seq | 985 | |||||
NBP_allele | |||||||||
Status | Live | ||||||||
Affects | Gene | WBGene00011936 | |||||||
Transcript | T22H2.6b.1 | VEP_consequence | splice_donor_variant,coding_sequence_variant,5_prime_UTR_variant,intron_variant | ||||||
VEP_impact | HIGH | ||||||||
Intron_number | 1/4 | ||||||||
Exon_number | 1/5 | ||||||||
T22H2.6a.1 | VEP_consequence | splice_donor_variant,coding_sequence_variant,5_prime_UTR_variant,intron_variant | |||||||
VEP_impact | HIGH | ||||||||
Intron_number | 2/5 | ||||||||
Exon_number | 1-2/6 | ||||||||
Isolation | Mutagen | TMP/UV | |||||||
Genetics | Map | I | |||||||
Description | Phenotype | WBPhenotype:0000154 | Paper_evidence | WBPaper00038205 | |||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | The homozygous mutant had approximately 20% reduction in total number of progeny (Fig. S4C). | Paper_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000473 | Paper_evidence | WBPaper00061552 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | animals display adult onset paralysis | Paper_evidence | WBPaper00061552 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
Rescued_by_transgene | WBTransgene00026278 | ||||||||
EQ_annotations | Life_stage | WBls:0000041 | PATO:0000460 | Paper_evidence | WBPaper00061552 | ||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000885 | Paper_evidence | WBPaper00038205 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | Time 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_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0004015 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||
Curator_confirmed | WBPerson712 | ||||||||
Life_stage | WBls:0000003 | PATO:0000460 | Paper_evidence | WBPaper00038205 | |||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0002045 | Paper_evidence | WBPaper00038205 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | We 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_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
EQ_annotations | Life_stage | WBls:0000003 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||
Curator_confirmed | WBPerson712 | ||||||||
Phenotype_not_observed | WBPhenotype:0000039 | Paper_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | Homozygous 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_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000062 | Person_evidence | WBPerson7743 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | Classified as homozygous viable by the National Bioresource Project of Japan. | Person_evidence | WBPerson7743 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000100 | Paper_evidence | WBPaper00038205 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | We found that pgrn-1 mutations did not affect UV-induced germ cell death(Fig. 2B). | Paper_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0006796 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000520 | Paper_evidence | WBPaper00038205 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | The 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_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0001172 | Paper_evidence | WBPaper00038205 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | The 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_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
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_evidence | WBPaper00038205 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0005116 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||
Curator_confirmed | WBPerson712 | ||||||||
WBbt:0005666 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBbt:0005829 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBbt:0003681 | PATO:0000460 | Paper_evidence | WBPaper00038205 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
Disease_info | Models_disease | DOID:9255 | |||||||
Modifies_disease | DOID:332 | ||||||||
Models_disease_in_annotation | WBDOannot00000006 | ||||||||
WBDOannot00001271 | |||||||||
WBDOannot00001272 | |||||||||
WBDOannot00001273 | |||||||||
WBDOannot00001274 | |||||||||
WBDOannot00001275 | |||||||||
Modifies_disease_in_annotation | WBDOannot00001023 | ||||||||
WBDOannot00001024 | |||||||||
WBDOannot00001035 | |||||||||
WBDOannot00001038 | |||||||||
WBDOannot00001041 | |||||||||
Reference | WBPaper00047019 | ||||||||
WBPaper00038205 | |||||||||
WBPaper00061552 | |||||||||
Remark | 13245/13246-13592/13593 (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_evidence | WBPaper00041807 | |||||||
Method | NBP_knockout_allele |