Lipodystrophy is characterised by reduced lipid storage in adipose tissue and ectopic lipid storage in non-adipose tissue. Seipinnull larvae show reduced lipid storage in fat bodies and ectopic lipid droplets in the salivary glands.
mdyQX25 Seipinnull double mutant larvae show greatly reduced fat body lipid storage compared to either single mutant (an exacerbation of the lipodystrophy model in adipose tissue). However, the ectopic lipid storage phenotype seen in non-adipose tissue in Seipinnull single mutants is fully suppressed by mdyQX25 (a suppression of the lipodystrophy model in non-adipose tissue).
Overexpression of mdy (using mdyEY07280) restores fat body lipid storage levels to near wild-type in Seipinnull larvae (a suppression of the lipodystrophy model in adipose tissue). However, overexpression of mdy (using mdyEY07280) increases the ectopic lipid storage phenotype observed in non-adipose tissue in Seipinnull larvae (an exacerbation of the lipodystrophy model in non-adipose tissue).
Seipinnull mutant fat body cell clones have fewer and smaller lipid droplets than adjacent control cells. In addition, the mutant cells are smaller than the surrounding wild type cells. The salivary glands in Seipinnull mutants are similar in size to wild type.
The overall level of free fatty acids, especially C12:0 , C14:0 , C16:0 , C16:1 and C18:1 ) is greatly reduced in Seipinnull mutant third instar larvae.
Compared to wild-type, the calcium-dependent ATPase activity is significantly decreased in Seipinnull mutants.
After treatment with Thapsigargin (a Ca-P60A inhibitor) or Ionomycim (a calcium ionophore) in calcium-free solution, the rise in cytosolic calcium levels seen in Seipinnull mutant fat body cells is significantly lower than in wild type.
The basal ER calcium level is decreased in Seipinnull mutant fat cells compared to wild type. Cytosolic calcium concentration is increased.
Mutants have no noticeable behaviour defects.
Fat bodies of Seipinnull larvae and fat cells from young Seipinnull adults have significantly reduced lipid storage compared to wild type. This small lipid droplet phenotype is more sever under starvation conditions. The overall morphology of the fat body in Seipinnull mutants appears normal.
Total glyceride content in Seipinnull mutants is greatly reduced compared to controls.
The average weight of Seipinnull flies is lower than controls.
Under fed conditions, the amount of neutral lipids in oenocytes of Seipinnull animals is the same as wild type. Neutral lipids are higher in starved Seipinnull animals, but sill much lower than wild type.
Circulating glyceride levels in the hemolymph of Seipinnull mutants are much lower than in wild type.
Under starved conditions, 100% of Seipinnull flies die within 42 hours, whereas more than half of control flies survive for 48 hours.
The proventriculus and anterior midgut region of Seipinnull mutants contain abnormally large lipid droplets and more stored lipid, respectively, compared to controls.
Seipinnull mutants exhibit ectopic lipid droplets in the salivary gland, which normally lacks any visible lipid droplets.
Seipinnull mutant larvae have increased levels of total and most individual species of phosphatidic acid.
The salivary glands of Seipinnull mutant larvae have increased levels of total and several species of diacylglycerol.
In Seipinnull mutants, the level of triacylglycerol (TAG) is greatly reduced in the fat body, while the levels of several TAG species are significantly increased in salivary glands.
Seipinnull has salivary gland phenotype, enhanceable by minoEY00734/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, enhanceable by minoEY00734/Scer\GAL448Y
Seipinnull has fat body phenotype, enhanceable by mdyQX25
Seipinnull has lipid droplet phenotype, enhanceable by mdyQX25
Seipinnull has salivary gland phenotype, enhanceable by mdyEY07280/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, enhanceable by mdyEY07280/Scer\GAL448Y
Seipinnull has salivary gland phenotype, enhanceable by Cds1
Seipinnull has lipid droplet | ectopic phenotype, enhanceable by Cds1
Seipinnull has fat body phenotype, non-enhanceable by Lsd2KG00149
Seipinnull has lipid droplet phenotype, non-enhanceable by Lsd2KG00149
Scer\GAL4ppl.PP, Seipinnull has adult fat body phenotype, suppressible | partially by SERCAUAS.Tag:MYC, Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has lipid droplet phenotype, suppressible | partially by SERCAUAS.Tag:MYC, Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has adult fat body phenotype, suppressible | partially by RyRJF03381, Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has lipid droplet phenotype, suppressible | partially by RyRJF03381, Scer\GAL4ppl.PP
Seipinnull has fat body phenotype, suppressible by mdyEY07280/Scer\GAL4ppl.PP
Seipinnull has lipid droplet phenotype, suppressible by mdyEY07280/Scer\GAL4ppl.PP
Seipinnull has fat body phenotype, suppressible by Scer\GAL4ppl.PP/SCAPEY06708
Seipinnull has lipid droplet phenotype, suppressible by Scer\GAL4ppl.PP/SCAPEY06708
Seipinnull has salivary gland phenotype, suppressible by mdyQX25
Seipinnull has lipid droplet | ectopic phenotype, suppressible by mdyQX25
Seipinnull has salivary gland phenotype, suppressible by LpinGD14004/Scer\GAL4ppl.PP
Seipinnull has lipid droplet | ectopic phenotype, suppressible by LpinGD14004/Scer\GAL4ppl.PP
Seipinnull has salivary gland phenotype, suppressible by LpinGD14004/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, suppressible by LpinGD14004/Scer\GAL448Y
Seipinnull has salivary gland phenotype, suppressible by CdsEY08412/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, suppressible by CdsEY08412/Scer\GAL448Y
Seipinnull has fat body phenotype, suppressible by Scer\GAL4ppl.PP/Hsap\BSCL2UAS.cTa
Seipinnull has lipid droplet phenotype, suppressible by Scer\GAL4ppl.PP/Hsap\BSCL2UAS.cTa
Seipinnull has salivary gland phenotype, suppressible by Scer\GAL4ppl.PP/Hsap\BSCL2UAS.cTa
Seipinnull has lipid droplet | ectopic phenotype, suppressible by Scer\GAL4ppl.PP/Hsap\BSCL2UAS.cTa
Seipinnull has fat body phenotype, suppressible by Hsap\BSCL2S90L.UAS/Scer\GAL4ppl.PP
Seipinnull has lipid droplet phenotype, suppressible by Hsap\BSCL2S90L.UAS/Scer\GAL4ppl.PP
Seipinnull has salivary gland phenotype, suppressible by Hsap\BSCL2S90L.UAS/Scer\GAL4ppl.PP
Seipinnull has lipid droplet | ectopic phenotype, suppressible by Hsap\BSCL2S90L.UAS/Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has adult fat body phenotype, non-suppressible by ItprGD1676, Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has lipid droplet phenotype, non-suppressible by ItprGD1676, Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has adult fat body phenotype, non-suppressible by SERCAKum170.UAS, Scer\GAL4ppl.PP
Scer\GAL4ppl.PP, Seipinnull has lipid droplet phenotype, non-suppressible by SERCAKum170.UAS, Scer\GAL4ppl.PP
Seipinnull has salivary gland phenotype, non-suppressible by minoe01407a
Seipinnull has lipid droplet | ectopic phenotype, non-suppressible by minoe01407a
Seipinnull has salivary gland phenotype, non-suppressible by Agpat2GD3463/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, non-suppressible by Agpat2GD3463/Scer\GAL448Y
Seipinnull has salivary gland phenotype, non-suppressible by Agpat1GD3545/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, non-suppressible by Agpat1GD3545/Scer\GAL448Y
Seipinnull has salivary gland phenotype, non-suppressible by Agpat2GD3463/Agpat1GD3545/Scer\GAL448Y
Seipinnull has lipid droplet | ectopic phenotype, non-suppressible by Agpat2GD3463/Agpat1GD3545/Scer\GAL448Y
Seipinnull is an enhancer of lipid droplet | ectopic phenotype of Cds1
Seipinnull is an enhancer of fat body phenotype of mdyQX25
Seipinnull is an enhancer of salivary gland phenotype of Cds1
Expression of Ca-P60AScer\UAS.T:Hsap\MYC partially rescues the reduction in lipid droplet size seen in Seipinnull mutant fat body cells. The reduction in ionomycin-evoked cytosolic calcium release is also partially rescued.
Expression of Ca-P60AKum170.Scer\UAS does not rescue the reduction in lipid droplet size seen in Seipinnull mutant fat body cells.
Expression of RyRJF03381 under the control of Scer\GAL4ppl.PP significantly rescues the reduction in lipid droplet size and glyceride level seen in Seipinnull mutant fat body cells.
Expression of Itp-r83AGD1676 under the control of Scer\GAL4ppl.PP does not rescue the reduction in lipid droplet size seen in Seipinnull mutant fat body cells.
Fat body lipid storage in Seipinnull; Lsd-2KG00149 animals is similar to Seipinnull single mutants.
mdyQX25, Seipinnull mutant fat bodies show greatly reduced lipid storage compared to either single mutant.
Expression of either mdyEY07280 or SCAPEY06708 using Scer\GAL4ppl.PP suppresses the reduced lipid storage phenotype seen in Seipinnull fat bodies.
Overexpression of CG5508EY00734 using Scer\GAL448Y enhances the ectopic lipid storage phenotype in salivary glands of Seipinnull mutants.
Overexpression of mdyEY07280 using Scer\GAL448Y in a Seipinnull mutant background results in a massive ectopic lipid storage phenotype in salivary glands.
The ectopic lipid storage phenotype of Seipinnull mutants is fully suppressed by mdyQX25 or by expression of LpinGD14004 using either Scer\GAL4ppl.PP or Scer\GAL448Y.
The ectopic lipid storage phenotype of Seipinnull mutants is not suppressed by CG5508e01407a or by expression of fu12GD3463, CG3812GD3545 or fu12GD3463 and CG3812GD3545 together using Scer\GAL448Y.
CdsA1, Seipinnull double mutants exhibit a strong synergistic phenotype (compared to either single mutant) with respect to ectopic lipid droplets in the salivary gland.
The ectopic lipid storage phenotype of Seipinnull mutants is fully suppressed by expressing CdsAEY08412 using Scer\GAL448Y.
There is more phosphatidic acid in the salivary glands of CdsA1; Seipinnull mutants than in CdsA1 single mutants.
Lipid storage in the fat body is restored and ectopic lipid storage in the salivary gland is reversed in Seipinnull mutants with Hsap\BSCL2Scer\UAS.cTa or Hsap\BSCL2S90L.Scer\UAS driven by Scer\GAL4ppl.PP.
Seipinnull is rescued by Scer\GAL4ppl.PP/SeipinUAS.Tag:MYC
Seipinnull is rescued by Scer\GAL4Tub.PU/SeipinUAS.cTa
Seipinnull is rescued by Scer\GAL4ppl.PP/SeipinUAS.cTa
Seipinnull is rescued by Scer\GAL4Lsp2.PH/SeipinUAS.cTa
Seipinnull is rescued by Scer\GAL4Sgs3.PD/SeipinUAS.cTa
Seipinnull is rescued by SeipinΔC.UAS/Scer\GAL4ppl.PP
Seipinnull is partially rescued by SeipinΔN.UAS.Tag:MYC/Scer\GAL4ppl.PP
Seipinnull is partially rescued by SeipinΔCT.UAS.Tag:MYC/Scer\GAL4ppl.PP
Seipinnull is partially rescued by Scer\GAL4ppl.PP/SeipinUAS.cTa
Seipinnull is not rescued by Scer\GAL4ppl.PP/SeipinΔLT.UAS.Tag:MYC
Seipinnull is not rescued by Scer\GAL4Lsp2.PH/SeipinUAS.cTa
Seipinnull is not rescued by Scer\GAL4Sgs3.PD/SeipinUAS.cTa
Seipinnull is not rescued by SeipinΔC.UAS/Scer\GAL4ppl.PP
Expression of SeipinScer\UAS.T:Hsap\MYC under the control of Scer\GAL4ppl.PP rescues the lipid storage phenotype seen in Seipinnull mutant fat bodies.
Expression of SeipinΔN.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ppl.PP partially rescues the lipid storage phenotype seen in Seipinnull mutant fat bodies.
Expression of SeipinΔCT.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ppl.PP partially rescues the lipid storage phenotype seen in Seipinnull mutant fat bodies.
Expression of SeipinΔLT.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ppl.PP does not rescue the lipid storage phenotype seen in Seipinnull mutant fat bodies.
The reduction in total glyceride content of Seipinnull is rescued by expression of SeipinScer\UAS.cTa using Scer\GAL4tub.PU.
The reduction in average weight of Seipinnull flies can be fully rescued by expressing SeipinScer\UAS.cTa with Scer\GAL4tub.PU and partially rescued by expressing SeipinScer\UAS.cTa with Scer\GAL4ppl.PP.
Expression of SeipinScer\UAS.cTa using Scer\GAL4tub.PU reverts the starvation hypersensitivity of Seipinnull flies to control levels.
Expression of SeipinScer\UAS.cTa using Scer\GAL4ppl.PP rescues the lipid storage defects in the fat body and ectopic lipid storage in the salivary gland of Seipinnull mutants.
Expression of SeipinScer\UAS.cTa using Scer\GAL4Lsp2.PH rescues the lipid storage defects in the fat body but not in the salivary gland or in the gut of Seipinnull mutants.
Expression of SeipinScer\UAS.cTa using Scer\GAL4Sgs3.PD rescues the ectopic lipid droplet phenotype in the salivary gland but not the lipid storage defects in the fat body or the ectopic lipid storage in the gut of Seipinnull mutants.
Expression of SeipinΔC.Scer\UAS using Scer\GAL4ppl.PP fully rescues the reduced lipid storage phenotype in the fat body of Seipinnull mutants, but does not rescue the ectopic lipid droplet phenotype in the salivary gland.