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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.

Author information

1
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.
2
Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
3
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Turin University, 10126 Turin, Italy.
4
Laboratory for Chemical and Clinical Analysis and Microbiology, University Hospital, Cona, 44124 Ferrara, Italy.
5
Department of Biomedical and Specialty Surgical Sciences, Medical Genetic Unit, Ferrara University, 44121 Ferrara, Italy.
6
Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10065, USA.

Abstract

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.

PMID:
26097845
PMCID:
PMC4434229
DOI:
10.1155/2015/687635
[Indexed for MEDLINE]
Free PMC Article

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