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

Moore, Richard C., Redhead, Nicola J., Selfridge, Jim, Hope, James, Manson, Jean C. and Melton, David W. (1995) Double replacement gene targeting for the production of a series of mouse strains with different prion protein gene alterations. Bio/Technology, 13 (9). pp. 999-1004. ISSN 0733-222X

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	biotechnology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	02 Dec 2025 15:30
Last Modified:	10 Dec 2025 14:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101196
DOI:	10.1038/nbt0995-999

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