Analysis of behavioral and transcriptomic changes in Slc6a20a heterozygous- and homozygous-mutant mice

Abstract

SLC6A20A is a member of the SLC6A family, which transports different types of small molecules across the plasma membrane. SLC6A20A is known to transport proline, but recently it has recently been found that it additionally transports glycine, which is a co-agonist of NMDA receptors (NMDARs) that critically regulate brain development and function. Previous studies also revealed that the ambient glycine levels increase in the brain of Slc6a20a-heterozygous knockout mice, the event that leads to a significant elevation of synaptic transmission mediated by NMDA receptors. However, the behavioral impacts of Slc6a20a deletion in mice remained unclear. In this thesis, I found that Slc6a20a heterozygous and homozygous deletions in mice cause differential behavioral changes that accompany substantial transcriptomic changes. These results suggest that SLC6A20A regulates ambient glycine concentration, NMDAR function, and NMDAR-related behaviors in mice.