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Identifier 000351277
Title Διερεύνηση του ρόλου των πρωτεινών Fras1/Frem εκτός της βασικής μεμβράνης των επιθηλίων
Alternative Title Investigation of the role of Fras1/Frem proteins in areas other than the epithelial basement membrane
Author Παυλάκης, Ευάγγελος
Thesis advisor Χαλεπάκης, Γεώργιος
Abstract The Fras1/Frem gene family encodes for structurally similar proteins of the extracellular matrix, functionally correlated with embryonic dermal-epidermal adhesion as deduced from the appearance of sub-epidermal blisters in mouse mutants compromising the function of Fras1, Frem1 and Frem2 proteins. Throughout the wider examination of the role of Fras1/Frem proteins, we began exploring areas of possible function of these proteins, other than the epithelial basement membrane. While all Fras1/Frem proteins are co-localized in all embryonic epithelial basement membranes, Frem3 is the only member of the family which shows a differential localization pattern, being detected on blood vessels and peripheral nerves, surrounding blood cells in embryos and being present in all adult epithelial basement membranes. Towards the understanding of the biological role of Frem3, we accomplished the targeted inactivation of the Frem3 gene in the mouse, in co-operation with Dr Kamal Chowdhury (Max Planck Institute for Biophysical Chemistry, Gottingen, Germany). One of the first observations is that crosses between Frem3+/- mice do not result in living homozygous animals, from the embryonic day E4.5 onwards. Since E4.5 defines the point when the embryo is implanted in the uterine wall, it is possible that the homozygous mutants die at the blastocyst stage. Analysis of the heterozygous mice revealed a plethora of phenotypic features such as characteristics of ichthyosis, dermatitis, alopecia, orchitis and epididymitis. The latter have also resulted in sterility of a very high proportion of the Frem3+/- male mice. The aforementioned phenotypic characteristics are indicative of a general mechanism of autoimmunity. Future experiments will have to disclose the exact role of the machinery leading to autoimmunity as well as how the partial shortage of Frem3 may contribute to all that. Regarding Fras1, previous mRNA in situ experiments, carried out on adult mouse brain sections, revealed that Fras1 is expressed by areas of the brain which play an important role in processes such as the memory of emotional reactions. Fear conditioning experiments on adult Fras1-/- mice suggest that these mice do not have any memory of the fear, whilst at the same time immunohistochemical experiments using various markers, revealed disturbances on the number of glial cells.
Language Greek
Subject Astrocytes
Inflammation
Αστροκύτταρα
Επιθήλια
Φλεγμονή
Issue date 2009-11-26
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/c/f/4/metadata-dlib-88429baefa8359257487b24d967f8ed6_1259045377.tkl Bookmark and Share
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