A targeting vector was designed to replace the coding sequence of the atonal homolog 1 (Atoh1) gene with a modified Cre-recombinase-progesterone receptor fusion protein (Cre-PR), abolishing gene function. Homozygous Math1Cre*PR mice die before birth due to central respiratory failure. Heterozygous mice are viable,fertile, and normal in size. The Math1Cre*PR/+ allele has expression of the Cre*PR fusion protein under control of the Math1 promoter/enhancer elements. Cre*PR fusion gene activity is inducible; observed only 6-12 hours after administration of RU486, a competitive progesterone receptor antagonist. As such, when Math1Cre*PR/+ mice are bred with mice containing loxP-flanked sequence, RU486-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Math1-expressing cells of the offspring. As such Math1 is expressed in the hindbrain, specifically in the conscious proprioceptive nuclei of the cortex at E10.5, and in most unconscious proprioceptive lineages in the cerebellum at E12.5-E14.5. These mutant mice are useful for the studying the characterization and time of formation of Math1-expressing cell lineages, as well as genetic and developmental links between proprioception, interoception, hearing, and arousal.
