A LacZ-based transgenic mouse for detection of somatic gene repair events in vivo View Full Text


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Article Info

DATE

2004-09

AUTHORS

H D Nickerson, W H Colledge

ABSTRACT

Somatic gene repair of disease-causing chromosomal mutations is a novel approach for gene therapy. This method would ensure that the corrected gene is regulated by its endogenous promoter and expressed at physiological levels in the appropriate cell types. A reporter mouse, Gtrosa26(tm1Col), was generated by targeting a mutated LacZ gene to the Rosa26 locus in mouse embryonic stem (ES) cells. The LacZ gene contains a G to A point mutation, resulting in a Glu to Lys amino-acid substitution at position 461, which abrogates enzymatic activity. The gene is expressed in ES cells, primary embryonic fibroblasts, and in all tissues examined in the adult mouse, including the lung, liver, kidney, spleen, heart, brain and smooth muscle. This transgenic mouse will allow testing of gene repair strategies in vivo and identification of which cell types can be successfully targeted by chromosomal gene repair. Although low levels of gene repair were achieved in the ES cells used to generate the Gtrosa26(tm1Col) mouse, preliminary attempts at gene repair in vivo were unsuccessful, thus highlighting the difficulties that will have to be overcome to get this approach to work. More... »

PAGES

1351

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.gt.3302311

    DOI

    http://dx.doi.org/10.1038/sj.gt.3302311

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1020749101

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15229632


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