MouSensor: A Versatile Genetic Platform to Create Super Sniffer Mice for Studying Human Odor Coding

• Published in: Cell reports (Cambridge) 2016-07, Vol.16 (4), p.1115-1125
• Main Authors: D’Hulst, Charlotte, Mina, Raena B., Gershon, Zachary, Jamet, Sophie, Cerullo, Antonio, Tomoiaga, Delia, Bai, Li, Belluscio, Leonardo, Rogers, Matthew E., Sirotin, Yevgeniy, Feinstein, Paul
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified - genetics; Axons - physiology; Binding Sites - genetics; Female; Gene Expression Regulation, Developmental - genetics; Humans; Male; Mice; Mice, Transgenic; Odorants; Olfactory Bulb - physiology; Olfactory Mucosa - physiology; Olfactory Receptor Neurons - physiology; Receptors, Odorant - genetics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.06.047

Typically, ∼0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these “MouSensors.” In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 MouSensor. Moreover, a behavioral avoidance task demonstrates that specific odor detection thresholds are significantly decreased in multiple transgenic lines, expressing mouse or human ORs. We have developed a versatile platform to study gene choice and axon identity, to create biosensors with great translational potential, and to finally decode human olfaction. [Display omitted] •Odorant receptor expression can be controlled using a 21-bp gene choice enhancer•In vivo synaptopHluorin imaging shows functional glomerular activation in MouSensors•MouSensors show lower specific odorant detection thresholds•Human odorant receptors can be expressed using the MouSensor genetic platform D’Hulst et al. have increased the total number of neurons expressing specific mouse or human odorant receptors (ORs) in the nose of a mouse by genetically controlling OR gene choice. These MouSensors show lower specific odor detection thresholds and provide a platform to study OR gene expression and odor coding in vivo.