scholarly journals Phenotypic rescue by a bovine transgene in a Cu/Zn superoxide dismutase-null mutant of Drosophila melanogaster

1994 ◽  
Vol 14 (2) ◽  
pp. 1302-1307
Author(s):  
I Reveillaud ◽  
J Phillips ◽  
B Duyf ◽  
A Hilliker ◽  
A Kongpachith ◽  
...  

Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila melanogaster are male sterile, have a greatly reduced adult life span, and are hypersensitive to paraquat. We have introduced a synthetic bovine CuZnSOD transgene under the transcriptional control of the D. melanogaster 5C actin promoter into a CuZnSOD-null mutant of D. melanogaster. This was carried out by P-element-mediated transformation of the Drosophila-bovine CuZnSOD transgene into a CuZnSOD+ recipient strain followed by genetic crossing of the transgene into a strain carrying the CuZnSOD-null mutation, cSODn108. The resulting transformants express bovine CuZnSOD exclusively to about 30% of normal Drosophila CuZnSOD levels. Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnSOD-null mutant rescues male fertility and resistance to paraquat to apparently normal levels. However, adult life span is restored to only 30% of normal, and resistance to hyperoxia is 90% of that found in control flies. This striking differential restoration of pleiotropic phenotypes could be the result of a threshhold of CuZnSOD expression necessary for normal male fertility and resistance to the toxicity of paraquat or hyperoxia which is lower than the threshold required to sustain a normal adult life span. Alternatively, the differential rescue of fertility, resistance to active oxygen, and life span might indicate different cell-specific transcriptional requirements for these functions which are normally provided by the control elements of the native CuZnSOD gene but are only partly compensated for by the transcriptional control elements of the actin 5C promoter.

1994 ◽  
Vol 14 (2) ◽  
pp. 1302-1307 ◽  
Author(s):  
I Reveillaud ◽  
J Phillips ◽  
B Duyf ◽  
A Hilliker ◽  
A Kongpachith ◽  
...  

Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila melanogaster are male sterile, have a greatly reduced adult life span, and are hypersensitive to paraquat. We have introduced a synthetic bovine CuZnSOD transgene under the transcriptional control of the D. melanogaster 5C actin promoter into a CuZnSOD-null mutant of D. melanogaster. This was carried out by P-element-mediated transformation of the Drosophila-bovine CuZnSOD transgene into a CuZnSOD+ recipient strain followed by genetic crossing of the transgene into a strain carrying the CuZnSOD-null mutation, cSODn108. The resulting transformants express bovine CuZnSOD exclusively to about 30% of normal Drosophila CuZnSOD levels. Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnSOD-null mutant rescues male fertility and resistance to paraquat to apparently normal levels. However, adult life span is restored to only 30% of normal, and resistance to hyperoxia is 90% of that found in control flies. This striking differential restoration of pleiotropic phenotypes could be the result of a threshhold of CuZnSOD expression necessary for normal male fertility and resistance to the toxicity of paraquat or hyperoxia which is lower than the threshold required to sustain a normal adult life span. Alternatively, the differential rescue of fertility, resistance to active oxygen, and life span might indicate different cell-specific transcriptional requirements for these functions which are normally provided by the control elements of the native CuZnSOD gene but are only partly compensated for by the transcriptional control elements of the actin 5C promoter.


Genome ◽  
1990 ◽  
Vol 33 (6) ◽  
pp. 867-872 ◽  
Author(s):  
Brian E. Staveley ◽  
John P. Phillips ◽  
Arthur J. Hilliker

We report here the isolation of a tandem duplication of a small region of the third chomosome of Drosophila melanogaster containing the Cu–Zn superoxide dismutase (cSOD) gene. This duplication is associated with a dosage-dependent increase in cSOD activity. The biological consequences of hypermorphic levels of cSOD in genotypes carrying this duplication have been investigated under diverse conditions of oxygen stress imposed by acute exposure to ionizing radiation, chronic exposure to paraquat, and the normoxia of standard laboratory culture. We find that a 50% increase in cSOD activity above the normal diploid level confers increased resistance to ionizing radiation and, in contrast, confers decreased resistance to the superoxide-generating agent paraquat. The duplication is associated with a minor increase in adult life-span under conditions of normoxia. These results reveal important features of the biological function of cSOD within the context of the overall oxygen defense system of Drosophila.Key words: gene duplication, paraquat, ionizing radiation, life-span.


Genetics ◽  
2002 ◽  
Vol 161 (2) ◽  
pp. 661-672
Author(s):  
Jingtao Sun ◽  
Donna Folk ◽  
Timothy J Bradley ◽  
John Tower

Abstract A transgenic system (“FLP-out”) based on yeast FLP recombinase allowed induced overexpression of MnSOD enzyme in adult Drosophila melanogaster. With FLP-out a brief heat pulse (HP) of young, adult flies triggered the rearrangement and subsequent expression of a MnSOD transgene throughout the adult life span. Control (no HP) and overexpressing (HP) flies had identical genetic backgrounds. The amount of MnSOD enzyme overexpression achieved varied among six independent transgenic lines, with increases up to 75%. Life span was increased in proportion to the increase in enzyme. Mean life span was increased by an average of 16%, with some lines showing 30-33% increases. Maximum life span was increased by an average of 15%, with one line showing as much as 37% increase. Simultaneous overexpression of catalase with MnSOD had no added benefit, consistent with previous observations that catalase is present in excess in the adult fly with regard to life span. Cu/ZnSOD overexpression also increases mean and maximum life span. For both MnSOD and Cu/ZnSOD lines, increased life span was not associated with decreased metabolic activity, as measured by O2 consumption.


Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 2295-2299 ◽  
Author(s):  
Atanu Duttaroy ◽  
Anirban Paul ◽  
Mukta Kundu ◽  
Amy Belton

AbstractA null mutation for the Sod2 gene, Sod2n283, was obtained in Drosophila melanogaster. Homozygous Sod2 null (Sodn283/Sodn283) adult flies survive up to 24 hr following eclosion, a phenotype reminiscent of mice, where Sod2–/– progeny suffer neonatal lethality. Sodn283/+ heterozygotes are sensitive to oxidative stress induced by paraquat treatment.


2002 ◽  
Vol 367 (2) ◽  
pp. 313-319 ◽  
Author(s):  
Katsuhisa INOUE ◽  
You-Jun FEI ◽  
Wei HUANG ◽  
Lina ZHUANG ◽  
Zhong CHEN ◽  
...  

Indy is a gene in Drosophila melanogaster which, when made dysfunctional, leads to an extension of the average adult life span of the organism. The present study was undertaken to clone the Indy gene-product and to establish its functional identity. We isolated a full-length Indy cDNA from a D. melanogaster cDNA library. The cDNA codes for a protein of 572 amino acids [(Drosophila Indy (drIndy)]. In its amino acid sequence, drIndy exhibits comparable similarity to the two known Na+-coupled dicarboxylate transporters in mammals; namely, NaDC1 (35% identity) and NaDC3 (34% identity). We elucidated the functional characteristics of drIndy in two different heterologous expression systems by using mammalian cells and Xenopus laevis oocytes. These studies show that drIndy is a cation-independent electroneutral transporter for a variety of tricarboxylic acid-cycle intermediates, with preference for citrate compared with succinate. These characteristics of drIndy differ markedly from those of NaDC1 and NaDC3, indicating that neither of these latter transporters is the mammalian functional counterpart of drIndy. Since drIndy is a transporter for tricarboxylic acid-cycle intermediates, dysfunction of the Indy gene may lead to decreased production of metabolic energy in cells, analogous to caloric restriction. This might provide the molecular basis for the observation that disruption of the Indy gene function in Drosophila leads to extension of the average adult life span of the organism.


Hereditas ◽  
2008 ◽  
Vol 112 (2) ◽  
pp. 117-127 ◽  
Author(s):  
ISAMU YONEMURA ◽  
MAYUMI ABE ◽  
RIKA ISHIDATE ◽  
TAKASHI ISHIYAMA ◽  
TOMIO MOTOYAMA ◽  
...  

Aging ◽  
2009 ◽  
Vol 1 (11) ◽  
pp. 903-936 ◽  
Author(s):  
Morris Waskar ◽  
Gary N. Landis ◽  
Jie Shen ◽  
Christina Curtis ◽  
Kevin Tozer ◽  
...  

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