Nature 355, 516 - 520 (06 February 1992); doi:10.1038/355516a0

Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox geneHox-#150;1.6

Osamu Chisaka, Teresa S. Musci & Mario R. Capecchi

Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.

Gene targeting in mouse embryo-derived stem cells has been used to generate mice with a disruption in the homeobox geneHox–1.6. Mice heterozygous at theHox-#150;1.6 locus appear normal, whereas Hox–1.6^-/Hox–1.6^- mice die at or shortly after birth. These homozygotes exhibit profound defects in the formation of the external, middle and inner ears as well as in specific hindbrain nuclei, and in cranial nerves and ganglia. The affected tissues lie within a narrow region along the anteroposterior axis of the mouse but are of diverse embryonic origin. The set of defects associated with the disruption of Hox-1.6 is distinct from and nonoverlapping with that of the closely linkedHox-1.5 gene. But both mutations cause loss, rather than homeotic transformation, of tissues and structures.

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