TARGETED DELETION OF THE MOUSE POU DOMAIN GENE BRN-3A CAUSES A SELECTIVE LOSS OF NEURONS IN THE BRAIN-STEM AND TRIGEMINAL GANGLION, UNCOORDINATED LIMB MOVEMENT, AND IMPAIRED SUCKLING

The Brn-3 subfamily of POU domain genes are expressed in sensory neuro ns and in select brainstem nuclei. Earlier work has shown that targete d deletion of the Brn-3b and Brn-3c genes produce, respectively, defec ts in the retina and in the inner ear. We show herein that targeted de letion of the Brn-3a gene results in defective suckling and in uncoord inated limb and trunk movements, leading to early postnatal death. Brn -3a (-/-) mice show a loss of neurons in the trigeminal ganglia, the m edial habenula, the red nucleus, and the caudal region of the inferior olivary nucleus but not in the retina and dorsal root ganglia. In the trigeminal and dorsal root ganglia, but not in the retina, there is a marked decrease in the frequency of neurons expressing Bm-Sb and Brn- 3c, suggesting that Brn-3a positively regulates Brn-3b and Brn-3c expr ession in somatosensory neurons. Thus, Brn-3a exerts its major develop mental effects in somatosensory neurons and in brainstem nuclei involv ed in motor control. The phenotypes of Brn-3a, Brn-3b, and Brn-3c muta nt mice indicate that individual Brn-3 genes have evolved to control d evelopment in the auditory, visual, or somatosensory systems and that despite differences between these systems in transduction mechanisms, sensory organ structures, and central information processing, there ma y be fundamental homologies in the genetic regulatory events that cont rol their development.