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 during embryonic and postnatal development of the CNS, but its effect on a sensory organ has not been studied in vivo. Therefore, we examined cochlear growth, differentiation, and maturation in Igf-1 gene knock-out mice at postnatal days 5 (P5), P8, and P20 by using stereological methods and immunohistochemistry. 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-deficient cochlear neurons showed increased caspase-3-mediated apoptosis, along with aberrant expression of the early neural markers nestin and Islet 1/2. Cochlear ganglion and fibers innervating the sensory cells of the organ of Corti presented decreased levels of neurofilament and myelin P(0) in P20 mouse mutants. In addition, an abnormal synaptophysin expression in the somata of cochlear ganglion neurons and sensory hair cells suggested the persistence 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 severely affects postnatal survival, differentiation, and maturation of the cochlear ganglion cells and causes abnormal innervation of the sensory cells in the organ of Corti.
Camarero
G
G
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain.
Avendano
C
C
Fernandez-Moreno
C
C
Villar
A
A
Contreras
J
J
de Pablo
F
F
Pichel
J G
JG
Varela-Nieto
I
I
D000375:Aging / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000235:genetics; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D003051:Cochlea / Q000254:growth & development / Q000473:pathology; D015834:Cochlear Diseases / Q000235:genetics* / Q000473:pathology*; D007758:Ear, Inner / Q000002:abnormalities* / Q000254:growth & development* / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology*; D009925:Organ of Corti / Q000473:pathology; D010641:Phenotype; D013136:Spiral Ganglion / Q000473:pathology; D015996:Survival Rate; D013680:Tectorial Membrane / Q000473:pathology
D007334:Insulin-Like Growth Factor I