Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2.
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.
Hanks
M
M
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Canada.
Wurst
W
W
Anson-Cartwright
L
L
Auerbach
A B
AB
Joyner
A L
AL
D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000196:embryology; D002678:Chimera; D003433:Crosses, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D017880:Limb Deformities, Congenital; D008297:Male; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D013234:Stem Cells; D013249:Sternum / Q000002:abnormalities; D000099266:Engrailed 2 Protein
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000099266:Engrailed 2 Protein; C080330:En1 protein, mouse