Gene Targeting 
executing each of those pathways. The non- 
overlap of phenotypes associated with disrupting 
these two genes argues for their independent 
character. For example, if a nonredundant com- 
binatorial code of box genes is used to specify 
each cell type in a given region, then the com- 
bined presence of both of these gene products 
does not specify any tissue. 
Disruption of the hox-1.6 gene results in regionally restricted developmental defects, including 
formation of the ear, cranial nerves, and ganglia, as well as the brain stem. This is illustrated by 
these embryos of El 0.5 mice immunoreacted with a monoclonal antibody against the 155-kDa 
neurofilament protein, a) cowfro/ hox-1 .6"^/hox-l .6^ embryo; b, c) two mutant hox-l .6~/hox- 
1.6" embryos. 
Reprinted by permission from Chisaka, O., Musci, T.S., and Capecchi, M.R. 1992. Nature 
355:516-520. Copyright© 1992 Macmillan Magazines Limited. 
exhibit profound defects in the formation of the 
ear, hindbrain nuclei, and cranial nerves and gan- 
glia. The glossopharyngeal and vagus nerves are 
poorly developed, and the preganglionic connec- 
tions with the brain stem are not formed. 
In both hox-l. 5 and -7. 6 mutants, the affected 
tissues are formed by very different embryonic 
pathways, yet the two hox genes are involved in 
64 
