Partial FAM19A5 Deficiency in Mice Leads to Disrupted Spine Maturation, Hyperactivity, and an Altered Fear Response

ABSTRACT The FAM19A 5 polypeptide, encoded by the TAFA 5 gene, is evolutionarily conserved among vertebral species. This protein is predominantly expressed in the brain, highlighting its crucial role in the central nervous system. Here, we investigated the potential roles of FAM19A 5 in brain development and behavior using a FAM19A 5 -LacZ KI mouse model. This model exhibited a partial reduction in the FAM19A 5 protein level. FAM19A 5 -LacZ KI mice displayed no significant alterations in gross brain structure but alterations in dendritic spine distribution, with a bias toward immature forms. These mice also had lower body weights. Behavioral tests revealed that compared with their wild-type littermates, FAM19A 5 -LacZ KI mice displayed hyperactivity and a delayed innate fear response. These findings suggest that FAM19A 5 plays a role in regulating spine formation and maintenance, thereby contributing to neural connectivity and behavior.