Trabajo presentado en el Spanish Symposium on IGFs and Insulin 2022: Implications in Physiology and Disease, celebrado en Logroño (España) del 21 al 22 de abril de 2022., Human deficiency of insulin-like growth factor type 1 (IGF-1) causes a rare disorder (OMIM608747; ORPHA73272), which leads to sensorineural hearing loss and neurological disorders [1,2]. The Igf1-deficient mouse replicates this neurological phenotype syndrome, and shows impaired neuronal differentiation and increased apoptosis of auditory neurons [3,4]. IGF-1 is a hormone associated with decreased neuroinflammation [5] and increased cellular senescence, though molecular mechanisms involved are poorly understood [6]. In order to study IGF-1 deficiency and understand the alterations linked to neuronal loss, a cellular model of the human disease was generated in the murine neuroblastoma cell line N2a by using CRISPR/Cas9 technology. The crRNA:tracrRNA:Cas9 complex was transfected as a ribonucleoprotein and clones were isolated by limiting dilution. Sanger and next-generation sequencing confirmed Igf1 gene editing. Clones 4A10 and 2G3, with a mutation frequency above 90%, were selected for the study. Both clones, which differentially expressed IGF system factors and proinflammatory cytokines, showed alterations in bleomycin-induced senescence and increased resistance to cisplatin treatment. Chronic IGF-1 deficiency leads to changes in the response to ototoxic drugs such as cisplatin and bleomycin in neuroblastoma cells. These cell lines are an opportunity to unravel new molecular mechanisms of neuronal damage associated with chronic IGF1 deficiency., THEARPY-PID2020-115274RB-I00 funded by MCIN/AEI/10.13039/501100011033 and NITROPROHEAR (0551_PSL_6_E POCTEP FGCSIC/PSL-INTERREG/FEDER).