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 la
rge mid-hindbrain deletion, whereas En-2 mutants are viable, with cere
bellar defects. To determine whether these contrasting phenotypes refl
ect differences in temporal expression or biochemical activity of the
En proteins, En-1 coding sequences were replaced with En-2 sequences b
y gene targeting. This rescued all En-1 mutant defects, demonstrating
that the difference between En-1 and En-2 stems from their divergent e
xpression patterns.