title: Generation and Characterization of a Transgenic Mouse Carrying a Functional Human β -Globin Gene with the IVSI-6 Thalassemia Mutation.
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.
authors.affiliation: 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.
authors.forename: Giulia
authors.identifier: 0000-0002-9013-1738
authors.initials: G
authors.lastname: Breveglieri
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Nicoletta
authors.identifier: 0000-0001-9280-6017
authors.initials: N
authors.lastname: Bianchi
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.affiliation: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Salvatori
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zuccato
authors.affiliation: 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.
authors.forename: Lucia C
authors.initials: LC
authors.lastname: Cosenza
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Montagner
authors.affiliation: Department of Life Sciences and Biotechnology, Biochemistry and Molecular Biology Section, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Turin University, 10126 Turin, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Turin University, 10126 Turin, Italy.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.affiliation: Laboratory for Chemical and Clinical Analysis and Microbiology, University Hospital, Cona, 44124 Ferrara, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Carandina
authors.affiliation: Department of Biomedical and Specialty Surgical Sciences, Medical Genetic Unit, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Michele
authors.identifier: 0000-0003-1448-9516
authors.initials: M
authors.lastname: Rubini
authors.affiliation: Department of Biomedical and Specialty Surgical Sciences, Medical Genetic Unit, Ferrara University, 44121 Ferrara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Aiello
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Breda
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.affiliation: 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.
authors.forename: Alessia
authors.identifier: 0000-0002-7638-515X
authors.initials: A
authors.lastname: Finotti
mesh_terms: D000818:Animals; D001483:Base Sequence; D006115:Greece; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D007558:Italy; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D017354:Point Mutation; D012326:RNA Splicing; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics* / Q000473:pathology
chemical_list: D006454:Hemoglobins; D055544:beta-Globins