Recent studies have shown critical roles of neural leucine-rich-repeat (LRR)-containing transmembrane superfamily proteins in health and disease. Among them, proteins with LRR with no other recognizable extracellular domains (''LRR-only'' proteins such as Lrrtm1-4 and Slitrk1-6) are known to be essential for synaptogenesis or maintaining synaptic functions. One of the LRR-only group members, Lrtm2, is a protein with a signal peptide, 6 LRR repeats, a transmembrane domain and a short cytoplasmic tail. Lrtm2 protein was strongly detected in striatum, globus pallidus and substantia nigra pars reticulata in mouse brain, and the protein content increased in the postnatal development. To clarify its physiological role, we generated Lrtm2-deficient mice and analyzed their phenotypes. In behavioral test battery, Lrtm2-deficient mice exhibited abnormalities in exploratory behavior whereas there were no clear deficits in the other behavioral properties. We then examined monoamine contents in homogenates prepared from various brain parts using both 5 month-old and 13-20 months old mice. The analysis showed significant alterations of dopamine metabolites content and serotonin turnover rate in striatum and other regions. Prefrontal cortex showed age-dependent changes. These results indicated that Lrtm2 is essential for the control of monoamine dynamics and the higher brain function. Further investigation on Lrtm2 molecular function is in progress to clarify the molecular mechanism underlying Lrtm2-mediated control of brain monoamines.
