Nerve growth factor-regulated properties of sensory neurones in Oct-2 null mutant mice.
The POU-domain transcription factor Oct-2 is expressed in both B lymphocytes and sensory neurones, where its expression is regulated by nerve growth factor (NGF). In order to define a possible role for Oct-2 in neurotrophin signalling, we examined the expression of an NGF-regulated channel (capsaicin-evoked ion fluxes), neuropeptides (substance P, calcitonin gene-related peptide), structural proteins (neurofilaments and peripherin) and receptors (trks) in dorsal root ganglion neurones derived from perinatal transgenic mice containing a defective Oct-2 structural gene. Northern blots show that central nervous tissue contains a larger than normal (> 10 kb) mRNA transcript corresponding in size to an Oct-2 transcript encoding a defective protein. PCR analysis shows the absence of normal Oct-2 transcripts in dorsal root ganglia. In null mutants, capsaicin sensitivity, and neuropeptide and cytoskeletal protein expression were unaffected by the loss of Oct-2 expression. The number of sensory neurones and the gross morphology of CNS tissues that normally express high levels of Oct-2 were also examined and found to be normal in the null mutant. Heterozygous animals show normal thresholds of sensitivity to noxious heat and normal inflammatory responses. Oct-2 does not therefore play an essential role in the NGF responsiveness of sensory neurones in these animals.
Ninkina
N N
NN
Department of Anatomy and Developmental Biology, University College, London, UK.
Buchman
V L
VL
Akopian
A N
AN
Lawson
S N
SN
Yamamoto
M
M
Campbell
E
E
Corcoran
L
L
Wood
J N
JN
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D003433:Crosses, Genetic; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D050813:Octamer Transcription Factor-2; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009414:Nerve Growth Factors; D050813:Octamer Transcription Factor-2; D016376:Oligonucleotides, Antisense; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors; D002211:Capsaicin; D002118:Calcium