RESUMO
G9a is essential for dendritic plasticity and is associated with neurological disorders. The possible relationship between age-related hearing loss and G9a expression in the auditory cortex has not been fully explored. This study aimed to understand the expression patterns of G9a-mediated histone methylations in the auditory cortex during aging. Using immunofluorescence and western blotting, we demonstrated that a significant reduction in G9a expression observed in the auditory cortex of 24-month-old rats compared to 3-month-old rats, was associated with remarkable hearing threshold elevation and hair cell loss. Correspondingly, histone H3 lysine 9 (H3K9) mono- and dimethylation (marked by H3K9me1 and H3K9me2, respectively), which were regulated by G9a activity, also evidently decreased during aging. These findings, which merit further investigation, suggest a possible association between G9a-mediated histone methylations and central age-related hearing disorders.
Assuntos
Córtex Auditivo/metabolismo , Histona-Lisina N-Metiltransferase/genética , Proteínas do Tecido Nervoso/genética , Presbiacusia/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Limiar Auditivo , Regulação para Baixo , Regulação da Expressão Gênica , Células Ciliadas Auditivas/patologia , Código das Histonas , Histona-Lisina N-Metiltransferase/biossíntese , Histonas/metabolismo , Masculino , Metilação , Modelos Animais , Proteínas do Tecido Nervoso/biossíntese , Presbiacusia/metabolismo , Presbiacusia/patologia , Processamento de Proteína Pós-Traducional , Ratos , Ratos Sprague-DawleyRESUMO
Previous studies have identified ~50 genes that contribute to non-syndromic autosomal dominant sensorineural deafness (DFNA). However, in numerous families with hearing loss, the specific gene mutation remains to be identified. In the present study, the clinical characteristics and gene mutations were analyzed in a Chinese pedigree with hereditary hearing loss. The clinical characteristics of the family members were assessed and a detailed audiology function examination was performed. Whole-exome sequencing (WES) was performed to identify the gene mutation responsible for the hearing loss. Sanger sequencing was used to verify the candidate mutation detected in the family. The family consisted of 31 members, seven of whom were diagnosed with sensorineural deafness of varying degrees. No mutation was identified by the general deafness gene chip. However, a novel heterozygous mutation in exon 3 (c.152C>T; Pro51Leu) of the gene crystallin µ (CRYM) was identified by WES. This result was further verified by Sanger sequencing. Co-segregation of genotypes and phenotypes suggested that this novel mutation was instrumental for the hearing loss/DFNA. In conclusion, the present study identified a novel pathogenic mutation, NM_001888.5(CRYM): c.152C>T(Pro51Leu), associated with DFNA. This mutation has not been reported previously and further functional studies are warranted.