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Publication : Double replacement gene targeting for the production of a series of mouse strains with different prion protein gene alterations.

First Author  Moore RC Year  1995
Journal  Biotechnology (N Y) Volume  13
Issue  9 Pages  999-1004
PubMed ID  9636277 Mgi Jnum  J:29021
Mgi Id  MGI:76549 Doi  10.1038/nbt0995-999
Citation  Moore RC, et al. (1995) Double replacement gene targeting for the production of a series of mouse strains with different prion protein gene alterations. Biotechnology 13(9):999-1004
abstractText  We have developed a double replacement gene targeting strategy which enables the production of a series of mouse strains bearing different subtle alterations to endogenous genes. This is a two-step process in which a region of the gene of interest is first replaced with a selectable marker to produce an inactivated allele, which is then re- targeted with a second vector to reconstruct the inactivated allele, concomitantly introducing an engineered mutation. Five independent embryonic stem cell lines have been produced bearing different targeted alterations to the prion protein gene, including one which raises the level of expression. We have constructed mice bearing the codon 101 proline to leucine substitution linked to the human familial prion disease, Gerstmann- Straussler-Scheinker syndrome. We anticipate that this procedure will have applications to the study of human inherited diseases and the development of therapies.
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