Hemochromatosis type 3 animal models
Aree / Gruppi di ricerca
Partecipanti al progetto
Descrizione del progetto
Type 3 hereditary hemochromatosis (HH) is caused by mutations in transferrin receptor 2 (TFR2) gene. Two alternative transcripts of TFR2 have been reported, alpha and beta. Tfr2 proteins are members of the transferrin receptor family, showing moderate homology to transferrin receptor (Tfrc) and are able to bind transferrin although with a lower affinity than that of Tfrc. TFR2 alpha mRNA and protein is highly expressed in the liver but also in other organs while TFR2 beta is particular expressed in different tissues reticulo-endothelial cells. TFR2 alpha expression is modulated by transferrin and its trafficking is regulated by Fe2Tf, since it increases Tfr2 amount on the cells surface inhibiting its lysosomal degradation and favouring receptor recycling.
The Tfr2 mouse models available at the Department of Clinical and Biological Science, University of Torino, present a very specific Tfr2 gene inactivation that takes in account the function of the second Tfr2 isoform (Tfr2 beta), that is significantly produced in the reticulo-endothelial cells. In particular, the model that will be utilized in this collaborative project (Tfr2 KI) is a Tfr2AlfpCre mouse model with a germinal inactivation of Tfr2 beta isoform.
Risultati e pubblicazioni
Pellegrino RM, Riondato F, Ferbo L, Boero M, Palmieri A, Osella L, Pollicino P, Miniscalco B, Saglio G,Roetto A. Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis. Biomed Res Int. 2017;2017:2408941.
Pellegrino RM, Boda E, Montarolo F, Boero M, Mezzanotte M, Saglio G, Buffo A, Roetto A. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse. Sci Rep. 2016;6:30725
Boero M, Pagliaro P, Tullio F, Pellegrino RM, Palmieri A, Ferbo L, Saglio G, De Gobbi M, Penna C, Roetto A. A comparative study of myocardial molecular phenotypes of two tfr2β null mice: role in ischemia/reperfusion. Biofactors. 2015;41:360-71
Nai A, Pellegrino RM, Rausa M, Pagani A, Boero M, Silvestri L, Saglio G, Roetto A, Camaschella C. The erythroid function of transferrin receptor 2 revealed by Tmprss6 inactivation in different models of transferrin receptor 2 knockout mice. Haematologica. 2014;99:1016-21