|Director : Mario M. Zakin (email@example.com)|
The Unit is studying the mechanisms of transcriptional regulation of genes that are expressed specifically in certain tissues. Two models are analysed: transferrin, a plasma protein responsible for the transport of iron in the organism and a cluster of genes encoding the apolipoproteins A-I/C-III/A-IV, involved in the metabolism and transport of lipids. These studies help to understand the role and the importance of the product of each gene analysed, in both normal and pathological conditions.
Human transferrin gene expression (Bruno Baron)
Transferrin (Tf), the iron-transport protein of vertebrate serum is sinthesized in hepatocytes but also in other cell-types including Sertoli cells and oligodendroctyes (OLs). We have previously found that Tf gene makes use of different combination of transcriptional factors in different subsets of cells to achieve tissue-specific expression. The laboratory is presently interested in the analysis of human Tf expression in the central nervous system (CNS), where the protein appears to have an influence on the early steps of myelinogenesis.
Transgenic mice specifically overexpressing hTf in the brain were obtained. These animals present a 30% increase of overall myelin content, distributed among its components as phospholipids, galactolipids and myelin proteins. Ultrastructural analysis by electronic microscopy shows that myelin of transgenic mice is normal in its compaction as well as in the number of wraps. In addition, transgenic animals present less signs of degeneration in the CNS than non-transgenic littermates and axons appear healthier. Behavior analysis has shown that transgenic animals have also a significant increase in motor coordination abilities. Now, we try to determine, by in situ hybridization and immunocytochemical experiments on primary OLs cultures, if Tf expression have an impact on proliferation and/or differentiation of OLs. Furthermore, we are developing the conditional invalidation of Tf in mice CNS using Cre-lox approach. Analysis of these animals will allow us to get a better insight of the Tf role in CNS development
The human apolipoprotein A-I/C-III/A-IV gene cluster (Mario M. Zakin)
The apolipoprotein A-I/C-III/A-IV gene cluster is involved in the metabolism and transport of lipids. We have generated transgenic mice expressing the human cluster. These mice provide an interesting model for studies of the regulation of the three genes in combination. They are also useful for studies of the function of the proteins encoded by the three genes. Expression of the human cluster induced hyperlipidemia but reduced atherogenesis in genetically modified mice lacking apolipoprotein E. We have recently demonstrated that the expression of the human gene cluster in mice also protects against atherogenesis in response to a high fat-high cholesterol diet. We have also generated transgenic mice expressing the human apolipoprotein A-IV. This expression reduced atherosclerotic lesions in mice lacking apolipoprotein E, without an increase in HDL cholesterol. The protection observed is accompanied by an in vivo reduction of the oxidation parameters, suggesting that human apolipoprotein A-IV acts in vivo as an antioxidant. Using our transgenic models, we are now analysing the interactions between infection, inflammation and atherosclerosis. Our first experiments show that LPS injected apoEo mice are a good model to study the influence of a chronical infection in lipid metabolism and atherosclerosis. We shall now analyse the possible protector role of apoA-IV during a chronical infection.
|Publications of the unit on Pasteur's references database|
|Office staff||Researchers||Scientific trainees||Other personnel|
Croullebois Elisabeth firstname.lastname@example.org
Baron Bruno IP – email@example.com
Duchange Nathalie - INSERM – firstname.lastname@example.org
Baroukh Nadine - Postdoc
Elfant David - University Student
Garcia-Otin Angel - Postdoc
Ostos Maria A. - Postdoc
Piaud Oriane – DEA Student
Recalde Delia - Postdoc
Saleh Maria-Carla - Postdoc
Pidoux Josette – Technician IP– email@example.com