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).
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).
da Cunha
Anderson F
AF
Hematology and Hemotherapy Center, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil. anderf@ufscar.br
Brugnerotto
Ana F
AF
Corat
Marcus A Finzi
MA
Devlin
Emily E
EE
Gimenes
Ana P
AP
de Melo
Mônica Barbosa
MB
Passos
Luiz A Corrêa
LA
Bodine
David
D
Saad
Sara T O
ST
Costa
Fernando F
FF
D000755:Anemia, Sickle Cell / Q000235:genetics; D000818:Animals; D001938:Brazil; D005319:Fetal Hemoglobin / Q000032:analysis / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D019076:Transgenes; D017086:beta-Thalassemia / Q000235:genetics; D055545:gamma-Globins / Q000096:biosynthesis*
D012333:RNA, Messenger; D055545:gamma-Globins; D005319:Fetal Hemoglobin