Generation and characterization of a transgenic mouse carrying a functional human β-globin gene with the IVSI-6 thalassemia mutation

Mouse models that carry mutations causing thalassemia represent a suitable tool to test in vivo new mutation-specific therapeutic approaches. Transgenic mice carrying the -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- -IVSI-6) carrying the IVSI-6 thalassemia point mutation within the human -globin gene. In the TG--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 -globin mRNA is produced, giving rise to -globin production and formation of a humanmouse tetrameric chimeric hemoglobin mu-globin2/ hu-globin2 and, more importantly, (d) the aberrant -globin-IVSI-6 RNAs are present in blood cells. The TG--IVSI-6 mouse reproduces the molecular features of IVSI-6 -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 -globin RNA sequences, caused by the IVSI-6 mutation. These experiments are expected to be crucial for the development of a personalized therapy for -thalassemia.