A foreign β-globin gene in transgenic mice: Integration at abnormal chromosomal positions and expression in inappropriate tissues

Lacy, Elizabeth; Roberts, Sally; Evans, E. P.; Burtenshaw, M. D.; Costantini, F

doi:10.1016/0092-8674(83)90369-0

Cited by 241 publications

(68 citation statements)

References 45 publications

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“…Although initial reports from a number of laboratories described low levels of globin expression in transgenic mice comparable to that in in vitro experiments (12,25,42,47), one study (43) (14). High-level transcription of viral RNA requires the viral enhancer, and therefore, as expected, near normal levels of viral RNA are seen after differentiation of MEL cells infected with pSVX3(RO) but not with pSVX,Ben-.…”

Section: Resultsmentioning

confidence: 99%

Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector.

Cone¹,

Weber-Benarous²,

Baorto³

et al. 1987

Mol. Cell. Biol.

150

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We introduced a human 0-globin gene into murine erythroleukemia (MEL) MATERIALS AND METHODSPlasmid constructions. A detailed account of the construction of pSVX has been presented previously (6). pSVXenwas constructed by first digesting a single long terminal repeat (LTR)-containing plasmid completely with XbaI and partially with PvuIl and then religating the appropriate fragment after addition of SalI linkers. A fragment containing the deleted LTR was then introduced in place of the 3' LTR of pSVX. All P-globin vectors were constructed by inserting a BclI-linkered 3.0-kb human 3-globin fragment, from the HpaI site to the PstI site, into the BamHI site of pSVX or pSVXen-. The human ,-globin gene and the SP6 plasmids used for synthesis of probes complementary to mouse and human f-globin mRNAs were kindly provided by

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Section: Resultsmentioning

confidence: 99%

Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector.

Cone¹,

Weber-Benarous²,

Baorto³

et al. 1987

Mol. Cell. Biol.

150

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show abstract

“…Likewise, the presence of the simian virus 40 enhancer sequence in the PSV2 gpt vector may influence the expression of the inserted genes (40). However, chromosomal location and/or structure (41,42), the extent of flanking DNA sequence (24), and methylation (43) …”

Section: Introduction Of the Chicken Actin Genes Into Myogenic C2mentioning

confidence: 99%

Expression and regulation of chicken actin genes introduced into mouse myogenic and nonmyogenic cells.

Seiler-Tuyns¹,

Eldridge²,

Paterson³

1984

Proc. Natl. Acad. Sci. U.S.A.

105

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We have introduced the chicken genes for cytoplasmic 13-actin', cardiac a-actin, and skeletal a-actin into :2 cells, a murine myogenic cell line, and into L cells by using the simian virus 40-derived vector PSV2-gpt. In each selection, the entire population of transformed cells was analyzed for the expression and regulation of the actin genes by nuclease S1 assay and primer extension. This was compared to the expression of the vector marker Eco-gpt. The .8-actin gene is transcribed accurately and efficiently both in L-cells and in undifferentiated C2 cells.'In fused C2 cells, (8-actin transcripts decrease significantly in parallel with the endogenous level of mouse f-actin mRNA. Eco-gpt RNA levels remain essentially constant during myogenesis. The a-actin genes are correctly expressed at low levels in L cells but at significantly higher levels in the C2 cell background. Unlike the endogenous mouse a-actin gene, this level of expression does not change measurably with inyogenesis. The skeletal a-actin gene is expressed poorly in pre-and post-fusion C2 cells, displaying no induction with differentiation. These results suggest that the tissue specificity of expression is maintained but the'pattern of gene regulation for the sarcomeric actins is not. Factors in addition to the sequences flanking these genes are important for modulating gene expression during development. The decrease in the levels of g3-actin RNA during C2 cell differentiation provides a model system in which to'study gene repression during development.

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“…In the latter case, tissue-specific expression of growth hormone was not observed, but the production of growth hormone in different cells was not found to be detrimental to the mice. However, this approach is not universally successful and has not yet been reported to work for other genes such as globin (Lacy et al, 1983).…”

Section: Gene Therapymentioning

confidence: 99%

An appraisal of the application of recombinant DNA techniques to chromosome defects

Ellis¹,

Davies²

1985

Biochemical Journal

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A foreign β-globin gene in transgenic mice: Integration at abnormal chromosomal positions and expression in inappropriate tissues

Cited by 241 publications

References 45 publications

Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector.

Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector.

Expression and regulation of chicken actin genes introduced into mouse myogenic and nonmyogenic cells.

An appraisal of the application of recombinant DNA techniques to chromosome defects

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