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Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells that can still enter the germline after genetic manipulation in culture and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DAN can be used in culture to modify specifically the target locus. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways.
T Doetschman, and
R G Gregg, and
N Maeda, and
M L Hooper, and
D W Melton, and
S Thompson, and
O Smithies
November 1988,
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T Doetschman, and
R G Gregg, and
N Maeda, and
M L Hooper, and
D W Melton, and
S Thompson, and
O Smithies
July 1992,
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T Doetschman, and
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M L Hooper, and
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O Smithies
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T Doetschman, and
R G Gregg, and
N Maeda, and
M L Hooper, and
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O Smithies
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T Doetschman, and
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S Thompson, and
O Smithies
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O Smithies
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T Doetschman, and
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N Maeda, and
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D W Melton, and
S Thompson, and
O Smithies
January 2003,
Methods in molecular biology (Clifton, N.J.),
T Doetschman, and
R G Gregg, and
N Maeda, and
M L Hooper, and
D W Melton, and
S Thompson, and
O Smithies
January 2009,
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T Doetschman, and
R G Gregg, and
N Maeda, and
M L Hooper, and
D W Melton, and
S Thompson, and
O Smithies
January 2012,
Methods in molecular biology (Clifton, N.J.),
