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PMID:21826223

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Citation

Nakayama, M, Sato, H, Okuda, T, Fujisawa, N, Kono, N, Arai, H, Suzuki, E, Umeda, M, Ishikawa, HO and Matsuno, K (2011) Drosophila carrying pex3 or pex16 mutations are models of Zellweger syndrome that reflect its symptoms associated with the absence of peroxisomes. PLoS ONE 6:e22984

Abstract

The peroxisome biogenesis disorders (PBDs) are currently difficult-to-treat multiple-organ dysfunction disorders that result from the defective biogenesis of peroxisomes. Genes encoding Peroxins, which are required for peroxisome biogenesis or functions, are known causative genes of PBDs. The human peroxin genes PEX3 or PEX16 are required for peroxisomal membrane protein targeting, and their mutations cause Zellweger syndrome, a class of PBDs. Lack of understanding about the pathogenesis of Zellweger syndrome has hindered the development of effective treatments. Here, we developed potential Drosophila models for Zellweger syndrome, in which the Drosophila pex3 or pex16 gene was disrupted. As found in Zellweger syndrome patients, peroxisomes were not observed in the homozygous Drosophila pex3 mutant, which was larval lethal. However, the pex16 homozygote lacking its maternal contribution was viable and still maintained a small number of peroxisome-like granules, even though PEX16 is essential for the biosynthesis of peroxisomes in humans. These results suggest that the requirements for pex3 and pex16 in peroxisome biosynthesis in Drosophila are different, and the role of PEX16 orthologs may have diverged between mammals and Drosophila. The phenotypes of our Zellweger syndrome model flies, such as larval lethality in pex3, and reduced size, shortened longevity, locomotion defects, and abnormal lipid metabolisms in pex16, were reminiscent of symptoms of this disorder, although the Drosophila pex16 mutant does not recapitulate the infant death of Zellweger syndrome. Furthermore, pex16 mutants showed male-specific sterility that resulted from the arrest of spermatocyte maturation. pex16 expressed in somatic cyst cells but not germline cells had an essential role in the maturation of male germline cells, suggesting that peroxisome-dependent signals in somatic cyst cells could contribute to the progression of male germ-cell maturation. These potential Drosophila models for Zellweger syndrome should contribute to our understanding of its pathology.

Links

PubMed PMC3149631 Online version:10.1371/journal.pone.0022984

Keywords

Animals; Brain/metabolism; Cell Line; Disease Models, Animal; Drosophila; Drosophila Proteins/genetics; Female; Male; Membrane Proteins/genetics; Microscopy, Electron; Motor Activity/genetics; Motor Activity/physiology; Mutation; Peroxisomes/metabolism; Zellweger Syndrome/genetics; Zellweger Syndrome/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q9VPB9

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VPB9

involved_in

GO:0007031: peroxisome organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VPB9

involved_in

GO:0042760: very long-chain fatty acid catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VUL8

involved_in

GO:0007031: peroxisome organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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