TMEM132D – a putative cell adhesion molecule involved in panic disorder

A recent association study analyzing panic disorder identified single nucleotide polymorphisms (SNPs) in TMEM132D. In a mouse model of extremes in trait anxiety, anxiety-related behaviour was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex. Screening for sites and motifs suggests a role of TMEM132D in cell adhesion but until now its function is unclear. The aim of this study is to investigate the function of TMEM132D as a new candidate gene using in vitro and in vivo approaches. Expression of a TMEM132D-GFP fusion protein in HEK cells confirmed its predicted localization in the cellular membrane. Overexpression significantly increased the number of filopodia-like structures. Additionally, we observed a strong colocalization of TMEM132D with actin filaments as shown by phalloidin staining. The expression pattern of Tmem132d in the brain of wild-type animals at different postnatal stages and in adult mice was analyzed by in situ hybridization (ISH). Conditional knock-out (KO) mice are currently established using embryonic stem cell clones received from the German Genetrap Consortium (GGTC) based on a conditional gene trapping approach. Specific expression of the LacZ reporter gene was analyzed by X-Gal staining confirming the results obtained by ISH. Colocalization studies in these animals revealed expression of the LacZ protein with different neuronal markers. The primary characterization and behavioural analysis of KO mice is in progress.