Erythroid-specific Expression of Human Beta-globin Genes in Transgenic Mice

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1985 Jul 1

PMID 2992937

Citations 150

Authors

T M Townes

J B Lingrel

H Y Chen

R L Brinster

R D Palmiter

Affiliations

Soon will be listed here.

Abstract

Transgenic mice carrying human beta-globin genes were produced by microinjecting linear DNA molecules containing cloned beta-globin genes with up to 4300 bp of 5'-flanking sequence and 1700 bp of 3'-flanking sequence. Most (15 of 20) of these transgenic mice expressed the human beta-globin genes in blood cells and the level of expression in some mice was comparable with that obtained from endogenous beta-globin genes. Human beta-globin gene expression appeared to be restricted to cells of the erythroid lineage and was first detected between 11 and 14 days of development, in parallel with mouse beta-globin. Constructs with as little as 48 bp of 5'-flanking sequence also appeared to be expressed appropriately. The mRNA transcripts had correct 5' ends and directed human beta-globin synthesis in reticulocyte lysates. Human beta-globin protein was detectable in mature erythrocytes from progeny of one of these mice. The frequency and extent of expression was severely depressed when the procaryotic vector DNA was not removed prior to microinjection.

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References

Ross J, Gielen J, Packman S, Ikawa Y, Leder P . Globin gene expression in cultured erythroleukemic cells. J Mol Biol. 1974; 87(4):697-714. DOI: 10.1016/0022-2836(74)90079-5. View

Gelinas R, Endlich B, Pfeiffer C, Yagi M, Stamatoyannopoulos G . G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemoglobin. Nature. 1985; 313(6000):323-5. DOI: 10.1038/313323a0. View

Chen C, Thomas Jr C . Recovery of DNA segments from agarose gels. Anal Biochem. 1980; 101(2):339-41. DOI: 10.1016/0003-2697(80)90197-9. View

Maxam A, Gilbert W . Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980; 65(1):499-560. DOI: 10.1016/s0076-6879(80)65059-9. View

Stalder J, Larsen A, Engel J, Dolan M, Groudine M, Weintraub H . Tissue-specific DNA cleavages in the globin chromatin domain introduced by DNAase I. Cell. 1980; 20(2):451-60. DOI: 10.1016/0092-8674(80)90631-5. View

Labarca C, Paigen K . A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980; 102(2):344-52. DOI: 10.1016/0003-2697(80)90165-7. View

Costantini F, Lacy E . Introduction of a rabbit beta-globin gene into the mouse germ line. Nature. 1981; 294(5836):92-4. DOI: 10.1038/294092a0. View

Wagner E, Stewart T, Mintz B . The human beta-globin gene and a functional viral thymidine kinase gene in developing mice. Proc Natl Acad Sci U S A. 1981; 78(8):5016-20. PMC: 320323. DOI: 10.1073/pnas.78.8.5016. View

Wagner T, Hoppe P, Jollick J, Scholl D, Hodinka R, Gault J . Microinjection of a rabbit beta-globin gene into zygotes and its subsequent expression in adult mice and their offspring. Proc Natl Acad Sci U S A. 1981; 78(10):6376-80. PMC: 349042. DOI: 10.1073/pnas.78.10.6376. View

10.

Brinster R, Chen H, Trumbauer M, Senear A, Warren R, Palmiter R . Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell. 1981; 27(1 Pt 2):223-31. PMC: 4883678. DOI: 10.1016/0092-8674(81)90376-7. View

11.

Grosveld G, de Boer E, Shewmaker C, Flavell R . DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982; 295(5845):120-6. DOI: 10.1038/295120a0. View

12.

Palmiter R, Chen H, Brinster R . Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell. 1982; 29(2):701-10. DOI: 10.1016/0092-8674(82)90186-6. View

13.

Dierks P, Ooyen A, Cochran M, Dobkin C, Reiser J, Weissmann C . Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983; 32(3):695-706. DOI: 10.1016/0092-8674(83)90055-7. View

14.

McGinnis W, Shermoen A, Heemskerk J, Beckendorf S . DNA sequence changes in an upstream DNase I-hypersensitive region are correlated with reduced gene expression. Proc Natl Acad Sci U S A. 1983; 80(4):1063-7. PMC: 393528. DOI: 10.1073/pnas.80.4.1063. View

15.

Ornitz D, Palmiter R, Hammer R, Brinster R, Swift G, MacDonald R . Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature. 1985; 313(6003):600-2. DOI: 10.1038/313600a0. View

16.

Chada K, Magram J, Raphael K, Radice G, Lacy E, Costantini F . Specific expression of a foreign beta-globin gene in erythroid cells of transgenic mice. Nature. 1985; 314(6009):377-80. DOI: 10.1038/314377a0. View

17.

Collins F, Weissman S . The molecular genetics of human hemoglobin. Prog Nucleic Acid Res Mol Biol. 1984; 31:315-462. DOI: 10.1016/s0079-6603(08)60382-7. View

18.

Clegg J, Naughton M, Weatherball D . Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok). J Mol Biol. 1966; 19(1):91-108. DOI: 10.1016/s0022-2836(66)80052-9. View

19.

Awdeh Z, Williamson A, Askonas B . Isoelectric focusing in polyacrylamide gel and its application to immunoglobulins. Nature. 1968; 219(5149):66-7. DOI: 10.1038/219066a0. View

20.

Lockard R, Lingrel J . Mouse hemoglobin messenger ribonucleic acid. Translational capacities of rabbit and duck reticulocyte cell-free systems programmed with mouse 9 S ribonucleic acid. J Biol Chem. 1972; 247(13):4174-9. View