C15232294T
L2767F | tefu-PB
L2429F
The difference between the annotated and the reported site of the amino acid change is due to the authors description of a 2429 residue protein, compared to the currently annotated 2767 residue polypeptide. Position of mutation on reference sequence inferred by FlyBase curator.
lethal | heat sensitive (with Df(3R)PG4)
adult thorax & chaeta | conditional ts (with Df(3R)PG4)
eye | heat sensitive (with Df(3R)PG4)
wing | heat sensitive (with Df(3R)PG4)
Mutant flies (raised at 18[o]C throughout development and then transferred to 25[o]C at 0-3 days of adulthood) show reduced climbing ability compared to wild type. In a countercurrent assay, 55% of the mutant flies are poor climbers, 30% moderate climbers and only 15% are good climbers (compared to wild-type values of 13% poor/moderate climbers and 87% good climbers). The results of two tests suggest that the difference in climbing ability between individual flies is due to differences in the severity of neurodegeneration. Firstly, flies which are poor climbers have significantly shorter longevity than good climbers, with the moderate climbers having intermediate longevity. Secondly, poor climbers have significantly more apoptotic cells in the brain than good climbers when assayed immediately after countercurrent separation (although there is no significant difference 4 days after countercurrent separation).
Homozygous and heterozygous adults have a significantly increased number of apoptotic cells in the brain compared to wild type, with the heterozygous flies have an intermediate level.
tefuatm-8 mutant flies develop to the adult stage when raised at 18[o]C and shifted to 25[o]C shortly after eclosion.
Homozygous and heterozygous tefuatm-8 mutant flies (raised at 18[o]C and shifted to 25[o]C shortly after eclosion) exhibit climbing defects. The phenotype is less severe in tefuatm-8/+ flies. Both homozygotes and heterozygotes are short lived compared to wild type controls.
At 7 days at 25[o]C scattered, small holes are observed in the neuropil of tefuatm-8/tefuatm-8 and tefuatm-8/+ mutant flies. After 17 days at 25[o]C the abundance and size of the holes is increased. Significantly more apoptotic (caspase 3 positive) neuronal and glial cells are seen at both time points in tefuatm-8 mutant flies in comparison with wild type and heterozygous controls.
At the restrictive temperature (25[o]C), tefuatm-8 mutants are recessive lethal.
Homozygous tefuatm-8 mutant females raised at the permissive temperature (18[[o]C) and then shifted to the restrictive temperature (25[o]C) exhibit an abnormally flattened or fragmented karyosome in 80% of cases.
In tefuatm-8 mutant germaria at the restrictive temperature, γ-His2Av staining persists into region 3 oocutes, consistent with a double strand break repair defects. However, in contrast to wild-type, the γ-His2Av staining in tefuatm-8 mutants exhibits more robust and continuous labeling, colocalizing with most of the chromosomes rather than appearing as foci.
At a restrictive temperature (25[o]C), tefuatm-8 mutants exhibit distinct γ-His2Av fci in nurse cells, indicating that tefu-deficient cells can restrict their double strand break response to the double strand break sites. The tefuatm-8 mutant nurse cells have a mean of 9.3 γ-His2Av foci, which is >2.5 times greater than the 3.6 γ-His2Av foci per nurse cell in wild-type.
At 24oC (semipermissive temperature), many tefuatm-8 animals can survive to adulthood, with a range of morphological defects, affecting structures such as the eye and wing. Analysis of tefuatm-8/Df(3R)PG4 animals indicates that the temperature sensitive period (TSP) for adult viability falls between the early third-larval instar and early pupal stage, the TSP for eye development is during the third larval instar and the TSP for wing and thoracic bristle development is during the pupal stage. 2 day old tefuatm-8/Df(3R)PG4 adults raised at the semipermissive temperature of 24oC have a much lower climbing ability than normal; average climbing ability of mutant males is only 11% that of controls, while the average climbing ability of mutant females is only 1% that of controls. The relative difference in climbing ability between mutant and control flies does not change over a period of 4 weeks when the flies are maintained at the restrictive temperature of 29oC. Third larval instar tefuatm-8 eye-antennal discs from animals raised at the restrictive temperature are generally smaller than control discs of a comparable age. The eye disc shows extensive apoptosis in the anterior region of the disc (in contrast to wild-type discs in which apoptotic cells are rare at this stage) and this is accompanied by obvious disorganisation of the differentiating neuronal cells. Third larval instar tefuatm-8/Df(3R)PG4 wing discs essentially lack mitotic cells 1 hour after exposure to γ irradiation (as is also seen in wild-type irradiated discs). Both control and mutant wing discs have increased numbers of apoptotic cells after irradiation. tefuatm-8/Df(3R)PG4 animals are extremely sensitive to irradiation; viability of mutant adults after third instar larvae have been exposed to γ radiation is dramatically reduced even at the lowest dose of 1Gy when larvae are raised at 24oC, even after taking into account the reduced viability at 24oC (semipermissive temperature).
tefuatm-8 has short lived phenotype, non-enhanceable by imdEY08573
tefuatm-8 has increased cell death | adult stage | semidominant phenotype, non-enhanceable by imdEY08573
tefuatm-8 has short lived phenotype, non-enhanceable by imdSDK
tefuatm-8 has increased cell death | adult stage | semidominant phenotype, non-enhanceable by imdSDK
tefuatm-8 has short lived phenotype, non-enhanceable by imd10191
tefuatm-8 has increased cell death | adult stage | semidominant phenotype, non-enhanceable by imd10191
tefuatm-8 has short lived phenotype, non-enhanceable by Dif1
tefuatm-8 has increased cell death | adult stage | semidominant phenotype, non-enhanceable by Dif1
tefuatm-8 has short lived phenotype, suppressible by RelE20
tefuatm-8 has short lived phenotype, suppressible by RelE38
tefuatm-8 has increased cell death | semidominant | adult stage phenotype, suppressible by RelE20
tefuatm-8 has increased cell death | semidominant | adult stage phenotype, suppressible by RelE38
tefuatm-8 has short lived phenotype, non-suppressible by imdEY08573
tefuatm-8 has short lived phenotype, non-suppressible by imdSDK
tefuatm-8 has short lived phenotype, non-suppressible by imd10191
tefuatm-8 has short lived phenotype, non-suppressible by Dif1
tefuatm-8 has increased cell death | semidominant | adult stage phenotype, non-suppressible by imdEY08573
tefuatm-8 has increased cell death | semidominant | adult stage phenotype, non-suppressible by imdSDK
tefuatm-8 has increased cell death | semidominant | adult stage phenotype, non-suppressible by imd10191
tefuatm-8 has increased cell death | semidominant | adult stage phenotype, non-suppressible by Dif1
tefuatm-8 has karyosome | heat sensitive phenotype, suppressible by mei-W684572
The karyosome morphology defects found in female tefuatm-8 mutants at the restrictive temperature of 25[o]C are suppressed in a mei-W684572 mutant background.
The karyosome morphology defects found in female tefuatm-8 mutants at the restrictive temperature of 25[o]C are suppressed in a mei-41D3 mutant background.
All γ-His2Av staining is eliminated in mei-W684572; tefuatm-8 double mutants, indicating that the abundant γ-His2Av staining in the tefuatm-8 mutant is dependent on the induction of meiotic double strand breaks.