[ genetic role of retinoic acid receptors in embryonic development: study of genetic mutations in retinoic acid receptors, resulting in tissue abnormalities]

Retinoic acid [RA] is a vitamin A derivative that exerts profound influences in vertebrate development and physiology. All-trans RA and 9-cis RA, are important regulators of embryonic development, cellular activity and tissue homeostasis. Their biological effects are mediated by two families of nuclear hormone receptors, retinoic acid [RAR] and retinoid X [RXR] receptors, which are ligand-dependent transcription factor. In the form of RAR-RXR or RXR-RXR dimers, the receptors act through binding to retinoic acid response elements [RAREs] present in the transcription regulatory region [promoter] of target genes. The identification of the pattern of expression of each isoform is crucial to our complete understanding of retinoid physiology. Compound null mutations of retinoic acid receptor [RAR] genes lead to lethality in uterus or shortly after birth and to numerous developmental abnormalities. The role of RXRs in the mediation of the developmental retinoid signal is less clear, because RXR beta and RXR gamma null mutant mice are viable and do not display any abnormality obviously related to a known function of vitamin A. Effects of retinoids in normal as well as abnormal development may be mediated by two members of retinoid receptors together, RARs and RXRs

[Molecular basis of proxysomal disorders in Zellweger syndrome]

Peroxisomes are organelles present in all eukaryotic cells from yeast to human cells. It is now well known that approximately fifty different biochemical reactions occur within the peroxisome, including synthesis of bile acids, cholesterol, ether-phospholipids [plasmalogens], docosahexaenoic acid and catabolism of certain fatty acids, particularly very long chain fatty acids [VLCFAs]. Proteins involved in peroxisomal function are known as peroxins. At least 29 peroxins are required for peroxisome membrane biogenesis, fission, and protein import. So far, mutations in 13 genes that encode peroxins are associated with human disease. Peroxisomal disorders currently falling into one of three groups; peroxisome biogenesis disorders [PBDs], peroxisomal multi-enzyme disorders, and peroxisomal single-enzyme disorders. Infantile Refsum's disease [IRD], neonatal adrenoleukodystrophy [NALD] and Zellweger's syndrome [ZS] are different variants of a group of congenital diseases known as peroxisome biogenesis disorders. These disorders are characterized by the absence of normal peroxisomes in the cells of the body which mostly are fatal. Here we describe molecular events that cause these deficiencies and we introduce current molecular approaches for diagnosis of these disorders like mutation analysis and fibroblasts characterization derived from the patients