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Hanks, M.* ; Wurst, W.* ; Anson-Cartwright, L.* ; Auerbach, A.B.* ; Joyner, A.L.*

Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2.

Science 269, 679-682 (1995)

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The related mouse Engrailed genes En-1 and En-2 are expressed from the one- and approximately five-somite stages, respectively, in a similar presumptive mid-hindbrain domain. However, mutations in En-1 and En-2 produce different phenotypes. En-1 mutant mice die at birth with a large mid-hindbrain deletion, whereas En-2 mutants are viable, with cerebellar defects. To determine whether these contrasting phenotypes reflect differences in temporal expression or biochemical activity of the En proteins, En-1 coding sequences were replaced with En-2 sequences by gene targeting. This rescued all En-1 mutant defects, demonstrating that the difference between En-1 and En-2 stems from their divergent expression patterns.

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