Peroxisome deficient invertebrate and vertebrate animal models.

Paul P Van Veldhoven,Myriam Baes

doi:10.3389/fphys.2013.00335

Abstract

Although peroxisomes are ubiquitous organelles in all animal species, their importance for the functioning of tissues and organs remains largely unresolved. Because peroxins are essential for the biogenesis of peroxisomes, an obvious approach to investigate their physiological role is to inactivate a Pex gene or to suppress its translation. This has been performed in mice but also in more primitive organisms including D. melanogaster, C. elegans, and D. rerio, and the major findings and abnormalities in these models will be highlighted. Although peroxisomes are generally not essential for embryonic development and organogenesis, a generalized inactivity of peroxisomes affects lifespan and posthatching/postnatal growth, proving that peroxisomal metabolism is necessary for the normal maturation of these organisms. Strikingly, despite the wide variety of model organisms, corresponding tissues are affected including the central nervous system and the testis. By inactivating peroxisomes in a cell type selective way in the brain of mice, it was also demonstrated that peroxisomes are necessary to prevent neurodegeneration. As these peroxisome deficient model organisms recapitulate pathologies of patients affected with peroxisomal diseases, their further analysis will contribute to the elucidation of still elusive pathogenic mechanisms.

Highlights

Absence of peroxisomes in man leads to a devastating disease, clinically known as the hepato-renal syndrome of Zellweger
CONCLUSION peroxisomes are not essential for cell functioning and survival, at the multicellular level they are indispensable as demonstrated by the different animal models treated in this chapter
Organogenesis seems to proceed normal, but the central nervous system appears sensitive to absence of peroxisomes

Summary

INTRODUCTION

Absence of peroxisomes in man leads to a devastating disease, clinically known as the hepato-renal syndrome of Zellweger. Upon silencing of 3,5- 2,4-dienoylCoA isomerase (encoded by Y25C1A.13), an enzyme required for degradation of polyunsaturated fatty acids, or silencing of the three ABC half-transporters (encoded by T02D1.5, C44B7.9, and C44B7.8), implicated in peroxisomal membrane translocation of fatty acids/acyl-CoAs, a similar phenotype is seen: no adult offspring three days after injection (Petriv et al, 2002) It should be noted, that silencing of peroxisomal thiolases, either the classical ones (encoded by T02G5.4 and T02G5.8) or SCP2-containing thiolase (encoded by daf-22), had no effect (Petriv et al, 2002). A drawback of this technique is, the November 2013 | Volume 4 | Article 335 | 9 www.frontiersin.org

Method

Findings

CONCLUSION