Partial FAM19A5 deficiency in mice leads to disrupted spine maturation, hyperactivity, and an altered fear response

The FAM19A5 polypeptide, encoded by the TAFA5 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 FAM19A5 in brain development and behavior using a FAM19A5-LacZ KI mouse model. This model exhibited a partial reduction in the FAM19A5 protein level. FAM19A5-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, FAM19A5-LacZ KI male mice displayed hyperactivity and a delayed innate fear response. These findings suggest that FAM19A5 plays a role in regulating spine maturation and maintenance, thereby contributing to neural connectivity and behavior.