Cochlear abnormalities in insulin-like growth factor-1 mouse mutants

• Published in: Hearing research 2002-08, Vol.170 (1), p.2-11
• Main Authors: Camarero, Guadalupe, Villar, M.Angeles, Contreras, Julio, Fernández-Moreno, Carmen, Pichel, José G., Avendaño, Carlos, Varela-Nieto, Isabel
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Animals, Newborn - physiology; Apoptosis; Auditory Pathways - pathology; Biological and medical sciences; Cell Count; Cell Size; Cochlea - abnormalities; Cochlea - growth & development; Cochlea - innervation; Cochlea - pathology; Cochlear neuron; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Ganglia - growth & development; Ganglia - metabolism; Ganglia - ultrastructure; Insulin-like growth factor 1; Insulin-Like Growth Factor I - genetics; Medical sciences; Mice; Mice, Knockout - genetics; Mouse knockout; Mutation - physiology; Myelin Sheath - ultrastructure; Nervous System - growth & development; Neurofilament Proteins - metabolism; Neurons, Afferent - pathology; Non tumoral diseases; Otorhinolaryngology. Stomatology; Postnatal development; Stereology; Vimentin - metabolism
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(02)00447-1

Insulin-like growth factor 1 (IGF-1) modulates inner ear cell proliferation, differentiation and survival in culture. Its function in human hearing was first evidenced by a report of a boy with a homozygous deletion of the Igf-1 gene, who showed severe sensorineural deafness [Woods et al., New Engl. J. Med. 335 (1996) 1363–1367]. To better understand the in vivo role of IGF-1 during inner ear differentiation and maturation, we studied the cochleae of Igf-1 gene knockout mice by performing morphometric stereological analyses, immunohistochemistry and electron microscopy on postnatal days 5 (P5), P8 and P20. At P20, but not at P5, the volumes of the cochlea and cochlear ganglion were significantly reduced in mutant mice, although the reduction was less severe than whole body dwarfism. A significant decrease in the number and average size of auditory neurons was also evident at P20. IGF-1-deficient cochlear neurons showed increased apoptosis, along with altered expression of neurofilament 200 kDa and vimentin. The eighth nerve, the cochlear ganglion and the fibers innervating the sensory cells of the organ of Corti of the P20 mouse mutants presented increased expression of vimentin, whereas the expression of neurofilament was decreased. In addition, the myelin sheath was severely affected in ganglion neurons. In conclusion, IGF-1 deficit in mice severely affects postnatal survival, differentiation and maturation of the cochlear ganglion cells.