ZnT3 expression levels are down-regulated in the brain of Mcoln1 knockout mice

• Main Authors: Jonathan Chacon, Lauren Rosas, Math P. Cuajungco
• Format: Article
• Language: English
• Published: BMC 2019-03-01
• Series: Molecular Brain
• Subjects: Zinc; ZnT3; Slc30a3; AP3; Ap3d1; TRPML1
• Online Access: http://link.springer.com/article/10.1186/s13041-019-0446-3
• ISSN: 1756-6606

Abstract Aim Zinc is a critical divalent cation in mammalian brain, but its concentration must be strictly-controlled. Within certain subsets of glutamatergic neurons, ZnT3 (encoded by the Slc30a3 gene) facilitates the transport and storage of zinc in synaptic vesicles. It has been previously reported that Slc30a3 mRNA levels are perturbed in numerous neurodegenerative disorders. Given the growing evidence of zinc dysregulation in another neurodegenerative disease known as Mucolipidosis IV (MLIV), we hypothesized that abnormal ZnT3 expression would be observed in the brain of MLIV mouse model. Elucidating the link between abnormal ZnT3 and zinc levels could reveal the neuropathological correlates between MLIV and other age-related brain disorders. Methods Total RNAs from cortical tissues of Mucolipin-1 knockout (Mcoln1 −/− KO) and Mcoln1 +/+ wild-type (WT) littermate control mice were analyzed for differential gene expression (DGE) using RNA sequencing (RNA-seq). Real-time quantitative PCR (qPCR) and Western blot techniques were used to validate the data. Results RNA-seq analysis showed a marked decrease in baseline levels of Slc30a3 mRNA in Mcoln1 −/− mice. Real-time qPCR and Western blot analyses confirmed that Slc30a3 transcripts and its protein levels were significantly reduced. Our observations add MLIV to a growing list of neurodegenerative diseases that parallels abnormal ZnT3 expression with zinc dyshomeostasis.