Résumé
Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Sujets)
Animaux , Souris , Rats , Animaux nouveau-nés , Protéines régulatrices de l'apoptose , Génétique , Métabolisme , Différenciation cellulaire , Physiologie , Prolifération cellulaire , Génétique , Cellules cultivées , Cuprizone , Toxicité , Maladies démyélinisantes , Métabolisme , Anatomopathologie , Embryon de mammifère , Régulation de l'expression des gènes au cours du développement , Génétique , Antigène KI-67 , Métabolisme , Souris de lignée C57BL , Protéine basique de la myéline , Métabolisme , Protéine protéolipidique myéline , Métabolisme , Gaine de myéline , Métabolisme , Oligodendroglie , Métabolisme , Protein-tyrosine kinases , Génétique , Métabolisme , Petit ARN interférent , Génétique , Métabolisme , Rat Sprague-DawleyRésumé
Objective To investigate the clinical application of multiplex allele-specific PCR assays for simultaneous detection of the mitochondrial 12S rRNA A1555G and C1494T mutations associated with aminoglycoside-induced hearing impairment.Methods Three standard plasmids of different genotypes (wild-type, A1555G mutant and C1494T mutant) were constructed for templates and allele-specific primers aiming directly at wild-type and mutant of mitochondrial DNA nt1555 and nt1494 were designed for developing a multiplex allele-specific PCR technique to detect the A1555G and C1494T mutations.Then the method was applied to clinical screening of 138 non-syndromic hearing loss subjects and confirmed by DNA sequencing.Results Multiplex allele-specific PCR was successfully applied to the detection of A1555G and C1494T mutations in a cohort of 138 Han Chinese genetically unrelated hearing-loss subjects.Finally, 11(7.97%) unrelated affected subjects harbored the A1555G and C1494T mutations in the 12S rRNA gene(10 cases for A1555G and 1 cases for C1494T), which was well consistent with results of DNA sequencing [7.97%(11/138), Kappa=1.000, P＜0.01].Conclusion This study indicates that the multiplex allele-specific PCR assay is useful, convenient and reliable in the detection of the A1555G and C1494T mutations, which could identify the subjects at risk and effectively prevent of aminoglycoside-induced hearing loss.