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Biomed Res Int. 2015;2015:687635. doi: 10.1155/2015/687635. Epub 2015 May 4.

Generation and Characterization of a Transgenic Mouse Carrying a Functional Human β -Globin Gene with the IVSI-6 Thalassemia Mutation.

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Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy ; Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of Thalassemia, Biotechnology Center, Ferrara University, 44121 Ferrara, Italy.
Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Turin University, 10126 Turin, Italy.
Laboratory for Chemical and Clinical Analysis and Microbiology, University Hospital, Cona, 44124 Ferrara, Italy.
Department of Biomedical and Specialty Surgical Sciences, Medical Genetic Unit, Ferrara University, 44121 Ferrara, Italy.
Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10065, USA.


Mouse models that carry mutations causing thalassemia represent a suitable tool to test in vivo new mutation-specific therapeutic approaches. Transgenic mice carrying the β-globin IVSI-6 mutation (the most frequent in Middle-Eastern regions and recurrent in Italy and Greece) are, at present, not available. We report the production and characterization of a transgenic mouse line (TG-β-IVSI-6) carrying the IVSI-6 thalassemia point mutation within the human β-globin gene. In the TG-β-IVSI-6 mouse (a) the transgenic integration region is located in mouse chromosome 7; (b) the expression of the transgene is tissue specific; (c) as expected, normally spliced human β-globin mRNA is produced, giving rise to β-globin production and formation of a human-mouse tetrameric chimeric hemoglobin (mu) α-globin2/(hu) β-globin2 and, more importantly, (d) the aberrant β-globin-IVSI-6 RNAs are present in blood cells. The TG-β-IVSI-6 mouse reproduces the molecular features of IVSI-6 β-thalassemia and might be used as an in vivo model to characterize the effects of antisense oligodeoxynucleotides targeting the cryptic sites responsible for the generation of aberrantly spliced β-globin RNA sequences, caused by the IVSI-6 mutation. These experiments are expected to be crucial for the development of a personalized therapy for β-thalassemia.

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