Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement, and impaired suckling.
The Brn-3 subfamily of POU domain genes are expressed in sensory neurons and in select brainstem nuclei. Earlier work has shown that targeted deletion of the Brn-3b and Brn-3c genes produce, respectively, defects in the retina and in the inner ear. We show herein that targeted deletion of the Brn-3a gene results in defective suckling and in uncoordinated limb and trunk movements, leading to early postnatal death. Brn-3a (-/-) mice show a loss of neurons in the trigeminal ganglia, the medial 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 Brn-3b and Brn-3c, suggesting that Brn-3a positively regulates Brn-3b and Brn-3c expression in somatosensory neurons. Thus, Brn-3a exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. The pheno-types of Brn-3a, Brn-3b, and Brn-3c mutant mice indicate that individual Brn-3 genes have evolved to control development 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 may be fundamental homologies in the genetic regulatory events that control their development.
Xiang
M
M
Department of Molecular Biology, Johns Hopkins University School Medicine, Baltimore, MD 21205, USA.
Gan
L
L
Zhou
L
L
Klein
W H
WH
Nathans
J
J
D000818:Animals; D001933:Brain Stem / Q000473:pathology* / Q000502:physiology; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005727:Ganglia, Spinal / Q000473:pathology / Q000502:physiology; D017353:Gene Deletion; D015698:Genomic Library; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009043:Motor Activity; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D013391:Sucking Behavior; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000473:pathology* / Q000502:physiology
D015342:DNA Probes; D004268:DNA-Binding Proteins; C494189:Pou4f1 protein, mouse; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors