This technology is a mouse cell line for conditional knockout of serotonin receptor 1a (5HT1AR) gene that can be used to study cell-type specific roles of 5HT1AR in antidepressant response, mood disorders, and anxiety.
Selective serotonin reuptake inhibitors (SSRIs) are one of the most widely used class of antidepressants. However, SSRIs act by elevating brain serotonin levels; a lack of understanding of how this modulates neuronal circuitry to mediate antidepressant responses has hindered the development of more specific and effective antidepressants. Serotonin receptor 1a (5HT1AR) levels and activity have been associated with depression, anxiety, and antidepressant responses, suggesting the gene plays a major role in SSRIs’ mechanisms. Since 5HT1AR is expressed in multiple cell types and regions in the brain, it is difficult to determine which specific receptor and its associated neural circuitry are critical for SSRIs’ antidepressant effects without cell-type or region-specific perturbation of 5HT1AR.
This technology is a mouse model engineered for the selective knockout of the serotonin receptor 1a (5HT1AR) gene in tissues or cells expressing the Cre recombinase protein. The 5HT1AR alleles are flanked by loxP sites, which allows Cre to excise the 5HT1AR exon and 3’ untranslated region. Following excision, a downstream fluorescent protein is expressed and regulated by the 5HT1AR promoter for visualization of 5HT1AR gene knockout. Before gene knockout, the genetically modified mice are indistinguishable from control mice in terms of behavior, response to the SSRI fluoxetine, and 5HT1AR binding activity. However, when the gene is knocked out in mature dentate gyrus granule cells, the mice no longer respond to fluoxetine.
This mouse line has been validated through crosses with Cre mouse lines and injections of lentiviral particles expressing Cre.
IR CU25138
Licensing Contact: Kristin Neuman