HIGH LEVELS OF HUMAN gamma-GLOBIN ARE EXPRESSED IN ADULT MICE CARRYING A TRANSGENE OF THE BRAZILIAN TYPE OF HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN ((A)gamma-195)

Author(s)

da Cunha, Anderson F. ; Brugnerotto, Ana F. ; Finzi Corat, Marcus A. ; Devlin, Emily E. ; Gimenes, Ana P. ; de Melo, Monica Barbosa ; Correa Passos, Luiz A. ; Bodine, David ; Saad, Sara T. O. ; Costa, Fernando F.

• Document type: Journal article
• Source: HEMOGLOBIN; v. 33, n. 6, p. 439-447, 2009.
• Web of Science Citations: 2

Abstract

Hereditary persistence of fetal hemoglobin (HPFH) is characterized by increased levels of Hb F during adult life. Nondeletional forms of HPFH are characterized by single base mutations in the (A)gamma and (G)gamma promoters, resulting in an increase of Hb F ranging from 3 to 20% in heterozygotes. Many point mutations in this region have been described, including the (A)gamma-195 (C>G) mutation that causes the Brazilian type of HPFH (HPFH-B). To better understand this mechanism, we have developed HPFH-B transgenic mice. mRNA levels of human gamma-globin of -195 transgenic mice were clearly higher when compared with control transgenic mice bearing a wild type sequence of the gamma promoter. Thus, our data indicate that the -195 mutation is the unique cause of elevation of Hb F in Brazilian HPFH. These results could provide us with an opportunity to study the modifying effects of the Hb F in the phenotype of sickle cell disease and beta-thalassemia (beta-thal). (AU)

• FAPESP's process: 02/13801-7 - Hereditary hemoglobin disorders: molecular genetics, clinical features and animal models with the production of transgenic animals
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants