Therapeutic manipulations of the mammalian cochlea, including cochlear gene
transfer, have been predominantly studied using the guinea pig as the expe
rimental model. With the significant developments in mouse genomics and the
availability of mutant strains of mice with well-characterized hearing los
s, the mouse justifiably will be the preferred animal model for therapeutic
manipulations. However, the potential advantages of the mouse model have n
ot been fully realized due to the surgical difficulty of accessing its smal
l cochlea. This study describes a ventral approach, instead of the routinel
y;sed postauricular approach in other rodents, for accessing the mouse midd
le and inner ear, and its application in cochlear gene transfer. This ventr
al approach enabled rapid and direct delivery of liposome-transgene complex
to the mouse inner ear while avoiding blood loss, facial nerve morbidity,
and mortality. Transgene expression at 3 days was detected in Reissner's me
mbrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pat
tern similar to that previously described in the guinea pig. The successful
access and delivery of material to the mouse cochlea and the replication o
f gene expression seen in the guinea pig demonstrated in this study should
promote the use of the mouse in future studies investigating targeted cochl
ear therapy. (C) 2001 Elsevier Science B.V. All rights reserved.