| First Author | Vadolas J | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 11 | Pages | 7399-405 |
| PubMed ID | 16421096 | Mgi Jnum | J:110556 |
| Mgi Id | MGI:3640628 | Doi | 10.1074/jbc.M512931200 |
| Citation | Vadolas J, et al. (2006) Humanized beta-thalassemia mouse model containing the common IVSI-110 splicing mutation. J Biol Chem 281(11):7399-405 |
| abstractText | Splicing mutations are common causes of beta-thalassemia. Some splicing mutations permit normal splicing as well as aberrant splicing, which can give a reduced level of normal beta-globin synthesis causing mild disease (thalassemia intermedia). For other mutations, normal splicing is reduced to low levels, and patients are transfusion-dependent when homozygous for the disease. The development of therapies for beta-thalassemia will require suitable mouse models for preclinical studies. In this study, we report the generation of a humanized mouse model carrying the common IVSI-110 splicing mutation on a BAC including the human beta-globin ((hu)beta-globin) locus. We examined heterozygous murine beta-globin knock-out mice ((mu)beta(th-3/+)) carrying either the IVSI-110 or the normal (hu)beta-globin locus. Our results show a 90% decrease in (hu)beta-globin chain synthesis in the IVSI-110 mouse model compared with the mouse model carrying the normal (hu)beta-globin locus. This notable difference is attributed to aberrant splicing. The humanized IVSI-110 mouse model accurately recapitulates the splicing defect found in comparable beta-thalassemia patients. This mouse model is available as a platform for testing strategies for the restoration of normal splicing. |
