Susanna Porcu

@article{marongiu_different_2016,

title = {Different switching patterns of β-thalassaemic mutations at the proximal and distal CACCC box of the human HBB (β-globin) gene},

author = {Maria F Marongiu and Susanna Porcu and Daniela Poddie and Dubravka Drabek and Ton {De Wit} and Antonio Cao and Maria S Ristaldi},

doi = {10.1111/bjh.13636},

issn = {1365-2141},

year  = {2016},

date = {2016-06-01},

journal = {British Journal of Haematology},

volume = {173},

number = {5},

pages = {794--797},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{manchinu_vivo_2014,

title = {In vivo activation of the human δ-globin gene: the therapeutic potential in β-thalassemic mice},

author = {Maria F Manchinu and Maria F Marongiu and Daniela Poddie and Carla Casu and Veronica Latini and Michela Simbula and Renzo Galanello and Paolo Moi and Antonio Cao and Susanna Porcu and Maria S Ristaldi},

doi = {10.3324/haematol.2012.082768},

issn = {1592-8721},

year  = {2014},

date = {2014-01-01},

journal = {Haematologica},

volume = {99},

number = {1},

pages = {76--84},

abstract = {β-thalassemia and sickle cell disease are widespread fatal genetic diseases. None of the existing clinical treatments provides a solution for all patients. Two main strategies for treatment are currently being investigated: (i) gene transfer of a normal β-globin gene; (ii) reactivation of the endogenous γ-globin gene. To date, neither approach has led to a satisfactory, commonly accepted standard of care. The δ-globin gene produces the δ-globin of hemoglobin A2. Although expressed at a low level, hemoglobin A2 is fully functional and could be a valid substitute of hemoglobin A in β-thalassemia, as well as an anti-sickling agent in sickle cell disease. Previous in vitro results suggested the feasibility of transcriptional activation of the human δ-globin gene promoter by inserting a Kruppel-like factor 1 binding site. We evaluated the activation of the Kruppel-like factor 1 containing δ-globin gene in vivo in transgenic mice. To evaluate the therapeutic potential we crossed the transgenic mice carrying a single copy activated δ-globin gene with a mouse model of β-thalassemia intermedia. We show that the human δ-globin gene can be activated in vivo in a stage- and tissue-specific fashion simply by the insertion of a Kruppel-like factor 1 binding site into the promoter. In addition the activated δ-globin gene gives rise to a robust increase of the hemoglobin level in β-thalassemic mice, effectively improving the thalassemia phenotype. These results demonstrate, for the first time, the therapeutic potential of the δ-globin gene for treating severe hemoglobin disorders which could lead to novel approaches, not involving gene addition or reactivation, to the cure of β-hemoglobinopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marongiu_reversible_2012,

title = {Reversible disruption of pre-pulse inhibition in hypomorphic-inducible and reversible CB1-/- mice},

author = {Maria Franca Marongiu and Daniela Poddie and Susanna Porcu and Maria Francesca Manchinu and Maria Paola Castelli and Valeria Sogos and Valentina Bini and Roberto Frau and Elisabetta Caredda and Maria Collu and Maria Serafina Ristaldi},

doi = {10.1371/journal.pone.0035013},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PloS One},

volume = {7},

number = {4},

pages = {e35013},

abstract = {Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes). Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout ((-/-)) mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1(-/-) mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1(-/-)) only in absence of doxycycline (Dox). In such mice, under Dox(+) or vehicle, as well as in wild-type (WT) and CB1(-/-), two endophenotypes motor activity (increased in animal models of schizophrenia) and pre-pulse inhibition (PPI) of startle reflex (disrupted in schizophrenia) were analyzed. Both CB1(-/-) and IRh-CB1(-/-) showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1(-/-) animals, was on the contrary highly and significantly disrupted only in Dox(+) IRh-CB1(-/-) mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1(-/-) mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1(-/-) mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in schizophrenia and in other psychiatric disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}