Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice

Insulin-like growth factor-1 (IGF-1) has been shown to play a key role duri ng embryonic and postnatal development of the CNS, but Its effect on a sens ory organ has not been studied in vivo. Therefore, we examined cochlear gro wth, differentiation, and maturation in Igf-1 gene knock-out mice at postna tal days 5 (P5), P8, and P20 by using stereological methods and immunohisto chemistry. Mutant mice showed reduction in size of the cochlea and cochlear ganglion. An immature tectorial membrane and a significant decrease in the number and size of auditory neurons were also evident at P20. IGF-1-defici ent cochlear neurons showed increased caspase-3-mediated apoptosis, along w ith aberrant expression of the early neural markers nestin and Islet 1/2. C ochlear ganglion and fibers innervating the sensory cells of the organ of C orti presented decreased levels of neurofilament and myelin P-o in P20 mous e mutants. In addition, an abnormal synaptophysin expression in the somata of cochlear ganglion neurons and sensory hair cells suggested the persisten ce of an immature pattern of synapses distribution in the organ of Corti of these animals. These results demonstrate that lack of IGF-1 in mice severe ly affects postnatal survival, differentiation, and maturation of the cochl ear ganglion cells and causes abnormal innervation of the sensory cells in the organ of Corti.