Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice

Abstract Reduced expression of glutamate decarboxylase 67 (GAD67), encoded by the Gad1 gene, is a consistent finding in postmortem brains patients with several psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder. The dysfunction GAD67 brain implicated pathophysiology these disorders; however, neurobiological consequences mature are not fully understood because homozygous knockout lethal newborn mice. We hypothesized that tetracycline-controlled gene expression/suppression system could be applied to develop global knockdown mice would survive into adulthood. In addition, provide new insights impact dysfunction. Here, we developed tTA/STOP?tetO biallelic knock-in using STOP?tetO tTA mice, compared them +/+ level protein treated doxycycline (Dox) was decreased approximately 90%. GABA content also Dox-treated open-field test, exhibited hyper-locomotor activity duration spent center region. acoustic startle responses were impaired These results suggest reduction elicits emotional abnormalities will useful for elucidating mechanisms abnormalities, such as anxiety symptoms associated disorders.