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Human G gamma and A gamma globin gene constructs containing the 3' A gamma enhancer show persistent fetal expression in transgenic mice. 1993

M P Harvey, and J Crosbie, and R J Trent
Molecular Genetics Laboratory, University of Sydney, NSW, Australia.

Transgenic mice were produced from two 13 kb constructs containing the fetal (gamma) globin genes. Each construct consisted of a G gamma globin gene linked to one of two alternative A gamma genes. The first construct contained a normal G gamma gene plus an A gamma gene with the -198 T-->C hereditary persistence of fetal haemoglobin (HPFH) mutation. In the second, a normal G gamma gene was linked to a A gamma gene with a -222 to -225 four base pair deletion in the promoter. This latter mutation has been associated with low A gamma expression in humans. Both A gamma genes in these constructs also contained the 3' flanking enhancer. The two different constructs showed expression throughout gestation from day 11 yolk sac, through the fetal period and for a variable time during the first three postnatal weeks. Thereafter, no expression of any of the gamma-globin genes was seen in adult erythroid tissues. Transcription from the normal G gamma and HPFH A gamma genes in the first construct paralleled each other in developmental timing, with a proportionate excess of A gamma more evident in later gestation. G gamma and A gamma mRNA transcripts from the normal G gamma + 4 bp deletional A gamma construct were unable to be distinguished because of a 3' G gamma-like conversion in the deletional A gamma gene. Combined gamma-globin expression from the two genes in this second construct was detectable until just after birth, as seen with the individual genes in the first construct.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004742 Enhancer Elements, Genetic Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter. Enhancer Elements,Enhancer Sequences,Element, Enhancer,Element, Genetic Enhancer,Elements, Enhancer,Elements, Genetic Enhancer,Enhancer Element,Enhancer Element, Genetic,Enhancer Sequence,Genetic Enhancer Element,Genetic Enhancer Elements,Sequence, Enhancer,Sequences, Enhancer
D005260 Female Females
D005319 Fetal Hemoglobin The major component of hemoglobin in the fetus. This HEMOGLOBIN has two alpha and two gamma polypeptide subunits in comparison to normal adult hemoglobin, which has two alpha and two beta polypeptide subunits. Fetal hemoglobin concentrations can be elevated (usually above 0.5%) in children and adults affected by LEUKEMIA and several types of ANEMIA. Hemoglobin F,Hemoglobin, Fetal
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D005914 Globins A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure. Globin

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