Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1

In the mouse, a mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) expresses one allele of one of the 1200 odorant receptor (OR) genes in the genome. The mechanisms that underlie the one receptor-one neuron rule remain poorly understood. A popular experimental paradigm for OR gene choice is to delete an OR coding region by gene targeting or in a transgene. Here we have applied this Delta OR paradigm to SR1, also known as MOR256-3 or Olfr124. This gene is expressed in OSNs of the MOE, and in similar to 50% of the OSNs of the septal organ. In heterozygous Delta SR1 mice, we observe an unprecedented biallelic expression rate of 30% at the SR1 locus. In homozygous Delta SR1 mice, we find a significant increase in the number of septal organ OSNs that undergo apoptosis. As a population, Delta SR1 OSNs project their axons to 81-85 glomeruli in each half of the OB, and coexpress at least 77 OR genes as evaluated by single-cell molecular analysis. There are no obvious or simple rules for the set of OR genes that are coexpressed with the Delta SR1 allele. The frequencies of coexpression are different for Delta SR1 OSNs in the septal organ compared to those in the MOE. We propose that there are as many as five scenarios for the fate of individual Delta SR1 OSNs. (C) 2013 Elsevier Inc. All rights reserved.