A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders.

[zellweger syndrome]

Human peroxisome biogenesis disorders are lethal genetic diseases in which abnormal peroxisome assembly compromises overall peroxisome and cellular function . Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes , notably lipid metabolism and the use of reactive oxygen species for detoxification . Using cultured cells , we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins ; required for peroxisome assembly and linked to peroxisome biogenesis disorders ), and confirmed that at least 13 of them are required for normal peroxisome assembly . We also demonstrate the relevance of Drosophila as a genetic model for the early developmental defects associated with the human peroxisome biogenesis disorders . Mutation of the PEX 1 gene is the most common cause of peroxisome biogenesis disorders and is one of the causes of the most severe form of the disease , Zellweger syndrome . Inherited mutations in Drosophila Pex 1 correlate with reproducible defects during early development . Notably , Pex 1 mutant larvae exhibit abnormalities that are analogous to those exhibited by Zellweger syndrome patients , including developmental delay , poor feeding , severe structural abnormalities in the peripheral and central nervous systems , and early death . Finally , microarray analysis defined several clusters of genes whose expression varied significantly between wild-type and mutant larvae , implicating peroxisomal function in neuronal development , innate immunity , lipid and protein metabolism , gamete formation , and meiosis .

Diseases
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Diseases presenting "common cause" symptom

achondroplasia

acute rheumatic fever

adrenomyeloneuropathy

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aniridia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

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congenital adrenal hyperplasia

congenital toxoplasmosis

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erdheim-chester disease

esophageal adenocarcinoma

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fabry disease

familial hypocalciuric hypercalcemia

hydrocephalus with stenosis of the aqueduct of sylvius

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

lamellar ichthyosis

legionellosis

liposarcoma

locked-in syndrome

malignant atrophic papulosis

neonatal adrenoleukodystrophy

neuralgic amyotrophy

pendred syndrome

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

scrub typhus

systemic capillary leak syndrome

thoracic outlet syndrome

typhoid

von hippel-lindau disease

wiskott-aldrich syndrome

zellweger syndrome

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