Deletion of the Sir2 coding region.
Deletion generated by targeted knockout, which removes the coding sequence precisely.
Sirt12A-7-11/Sirt12A-7-11 mutant flies are less sensitive to the sedating effects of acute ethanol exposure, and also show a marked decrease in sedation tolerance, but do not exhibit alterations in ethanol absorption or metabolism, as compared to controls. Wild type flies pre-exposed to ethanol vapor develop rapid ethanol preference given a choice of liquid food with and without added ethanol, but this preference fails to develop in Sirt12A-7-11/Sirt12A-7-11 mutants, in fact, these mutants are more likely to prefer ethanol-containing food when they have no pre-exposure to ethanol. Sirt12A-7-11/Sirt12A-7-11 mutants do not show a significant difference in aversion to quinine as compared to controls. Sirt12A-7-11/Sirt12A-7-11 flies show strongly reduced conditioned odor preference associated with ethanol intoxication, but no defects in olfactory acuity.
Sirt12A-7-11 homozygotes as well as Sirt12A-7-11/Df(2L)ED784 mutant adults have extra scutellar bristles.
Sirt12A-7-11/Df(2L)ED784 adults display ectopic wing vein material.
Sirt14.5/Sirt12A-7-11 adult males show significantly decreased survival under starvation conditions at 3 weeks (but not 2 weeks) old, compared to controls (relative feeding rate is similar to controls at 1 or 2 weeks old). Sirt14.5/Sirt12A-7-11 males fed ad libitum show significantly higher levels of glucose and glycogen (at 1 and 2 weeks old) and triglycerides (at 2 but not 1 weeks old) compared to wild type. In fasting conditions, mutants show significantly higher glucose levels (at 2 but not 1 week old), compared to wild type. Sirt14.5/Sirt12A-7-11 mutants are insulin resistant by 2 weeks of age.
Sirt12A-7-11 mutant adults show reduced survival upon starvation compared to wild-type controls.
Adult brains have a significant decrease in dopaminergic neuron number (especially in the DL1 cluster) in 30 day old Sirt12A-7-11/Sirt12A-7-11 flies. Climbing ability in Sirt12A-7-11/Sirt12A-7-11 is significantly worse and there is a significant reduction in ATP of the indirect flight muscle compared to wild type at 15 (but not 3) days old.
Homozygotes show no obvious morphological or behavioural defects.
At 60% ethanol vapor dose, Sir22A-7-11 flies show reduced sedation sensitivity, reduced sedation tolerance, and almost no increase in locomotor activity upon repeated ethanol exposure compared to controls. At 73% ethanol vapor dose, Sir22A-7-11 flies retain the latter phenotype, but exhibit normal sedation sensitivity and sedation tolerance.
Sir22A-7-11/Sir2NP1145 flies show almost no increase in locomotor activity upon repeated ethanol exposure compared to controls.
Sir22A-7-11 mutants have a similar frequency of single-strand annealing repair (SSA) compared to controls in a P{wIw.FRT} hemizygous assay to study DNA double-stranded break repair when assayed at 32oC or 38oC.
Heterozygous males do not have ectopic sex combs on the T2 or T3 legs.
Sirt12A-7-11 has visible | adult stage phenotype, enhanceable by N[+]/N55e11
Sirt12A-7-11 has visible | adult stage phenotype, enhanceable by DeltaRevF10/Dl[+]
Sirt12A-7-11 has decreased cell number | adult stage phenotype, non-enhanceable by Pink1B9
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of visible | adult stage phenotype of DeltaRevF10
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of visible | adult stage phenotype of N55e11
Sirt1[+]/Sirt12A-7-11 is an enhancer of visible | adult stage phenotype of N55e11
Sirt1[+]/Sirt12A-7-11 is an enhancer of visible | adult stage phenotype of H2
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of visible | adult stage phenotype of H2
Sir2[+]/Sirt12A-7-11 is an enhancer of visible | dominant | homeotic phenotype of Pcl11
Sir2[+]/Sirt12A-7-11 is an enhancer of visible | dominant | homeotic phenotype of Pc3
Sirt12A-7-11 has scutellar bristle | increased number phenotype, enhanceable by N[+]/N55e11
Sirt12A-7-11 has scutellar bristle | increased number phenotype, enhanceable by DeltaRevF10/Dl[+]
Sirt12A-7-11 has dorso-lateral dopaminergic neuron phenotype, non-enhanceable by Pink1B9
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of scutellar bristle | increased number phenotype of DeltaRevF10
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of scutellar bristle | increased number phenotype of N55e11
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of wing vein phenotype of N55e11
Sirt1[+]/Sirt12A-7-11 is an enhancer of wing vein phenotype of N55e11
Sirt1[+]/Sirt12A-7-11 is an enhancer of wing vein L5 phenotype of H2
Sirt12A-7-11/Sirt12A-7-11 is an enhancer of wing vein L5 phenotype of H2
Sir2[+]/Sirt12A-7-11 is an enhancer of mesothoracic leg phenotype of Pcl11
Sir2[+]/Sirt12A-7-11 is an enhancer of sex comb | ectopic phenotype of Pcl11
Sir2[+]/Sirt12A-7-11 is an enhancer of mesothoracic leg phenotype of Pc3
Sir2[+]/Sirt12A-7-11 is an enhancer of sex comb | ectopic phenotype of Pc3
Pc3, Sir2[+]/Sirt12A-7-11 has metathoracic leg phenotype
Pcl11, Sir2[+]/Sirt12A-7-11 has metathoracic leg phenotype
Pc3, Sirt12A-7-11 has metathoracic leg phenotype
Pcl11, Sirt12A-7-11 has metathoracic leg phenotype
The formation of extra scutellar bristles observed in each of the following single mutants: Sirt12A-7-11/Sirt12A-7-11, DlRevF10/+ and N55e11/+ is strongly enhanced in either Sirt12A-7-11/Sirt12A-7-11;DlRevF10/+ or N55e11/+;Sirt12A-7-11/Sirt12A-7-11 double mutants, which on average have around seven scutellar bristles (instead of the four normally found in wild-type flies).
Similarly, the severity (width) of the vein deltas phenotype characteristic for N55e11 heterozygotes is increased by hetero- or (more strongly) homozygosity of Sirt12A-7-11.
The shortening of the wing vein L5 observed H2 heterozygous adults is partially rescued by combination with one or (more strongly) two copies of Sirt12A-7-11.
Two copies of Hnf4T:Avic\GFP-SF,T:Zzzz\FLAG restores normal insulin signaling responses but does not rescue hyperglycemia and elevated glycogen levels in Sirt14.5/Sirt12A-7-11 flies.
Pink1B9/Y does not enhance dopaminergic neuron loss (in the DL1 cluster) in Sirt12A-7-11/Sirt12A-7-11 flies.
The frequency of ectopic sex combs seen in Pc3/+ males is increased by Sir22A-7-11; in Sir22A-7-11/+ ; Pc3/+ double heterozygous males, 98% of T2 legs and 61% of T3 legs have sex combs, while in Sir22A-7-11/Sir22A-7-11 ; Pc3/+ males, 99% of T2 legs and 78% of T3 legs have sex combs. The frequency of ectopic sex combs seen in Pcl11/+ males is increased by Sir22A-7-11; in Sir22A-7-11/+ ; Pcl11/+ double heterozygous males, 76% of T2 legs and 35% of T3 legs have sex combs. Eye colour: Sir22A-7-11/+ moderately, though consistently, impairs the silencing of the heterozygous wUbxPRE.2.2 transgene, resulting in a slight increase in eye pigmentation. Eye colour: flies homozygous for wUbxPRE.2.2 show a dramatic increase in eye pigmentation if they are also homozygous for Sir22A-7-11.
Sirt14.5/Sirt12A-7-11 is rescued by Sirt1UAS.cPa/Scer\GAL4r4
Sirt12A-7-11 is partially rescued by Scer\GAL4elav-C155/Sirt1UAS.DsRed(Unk)
Sirt14.5/Sirt12A-7-11 is not rescued by Sirt1UAS.cPa/Scer\GAL4Mef2.PR
Sirt14.5/Sirt12A-7-11 is not rescued by Sirt1UAS.cPa/Scer\GAL4Ilp2.215-1
Expression of Sirt1Scer\UAS.T:Disc\RFP under the control of Scer\GAL4elav-C155 fails to rescue the reduced ethanol sensitivity, but does rescue the reduced tolerance to repeated ethanol exposure seen in Sirt12A-7-11/Sirt12A-7-11 flies.
Expression of Sirt1Scer\UAS.cPa driven in the fat body by Scer\GAL4r4 (but not when driven by Scer\GAL4Mef2.PR or Scer\GAL4Ilp2.215-1) rescues insulin signaling in peripheral tissues of Sirt14.5/Sirt12A-7-11 flies.
H. Xie K. Golic