Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mice results in changes in axon morphology and extraglomerular fiber growth
Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mice results in changes in axon morphology and extraglomerular fiber growth
复制标题
生长相关蛋白 B-50/GAP-43 在转基因小鼠嗅觉神经元中的定向表达导致轴突形态和肾小球外纤维生长的变化
作者：
A. Holtmaat;P. Dijkhuizen;A. Oestreicher;HJ Romijn;NM Van der Lugt;A. Berns;F. Margolis;W. Gispen;J. Verhaagen
B-50/GAP-43是一种与神经生长相关的磷蛋白，被认为在神经元可塑性和神经纤维形成中起作用，因为它在发育和再生神经元以及生长锥中以高水平表达。使用含有在嗅觉标记蛋白（OMP）基因的调节元件控制下的B- 50/GAP-43的编码序列的构建体，产生转基因小鼠以研究B-50/GAP-43在一类通常不表达B-50/GAP-43的神经元（即成熟OMP阳性嗅觉神经元）中的定向表达的效果。嗅觉神经元具有有限的寿命，并且在整个成年期被新的神经元取代，所述新的神经元在其从该神经上皮的基底部分中的干细胞形成之后迁移到上皮的上隔室中。因此，初级嗅觉通路非常适合于研究B-50/GAP- 43在神经元迁移、寿命和神经纤维生长中的作用。我们发现，B-50/GAP-43在成年嗅觉神经元的表达结果在许多初级嗅觉轴突扩大的结束优先位于个别肾小球的边缘。此外，异位嗅神经纤维之间的肾小球神经元或密切接近血管经常观察到。这表明成熟嗅觉神经元中B-50/GAP-43的表达改变了它们对球中信号的反应。B-50/GAP-43转基因小鼠嗅神经元的迁移和寿命正常。这些观察结果为B-50/GAP-43在神经纤维形成和轴突形态学测定中的作用提供了直接的体内证据。
B-50/GAP-43, a neural growth-associated phosphoprotein, is thought to play a role in neuronal plasticity and nerve fiber formation since it is expressed at high levels in developing and regenerating neurons and in growth cones. Using a construct containing the coding sequence of B- 50/GAP-43 under the control of regulatory elements of the olfactory marker protein (OMP) gene, transgenic mice were generated to study the effect of directed expression of B-50/GAP-43 in a class of neurons that does not normally express B-50/GAP-43, namely, mature OMP-positive olfactory neurons. Olfactory neurons have a limited lifespan and are replaced throughout adulthood by new neurons that migrate into the upper compartment of the epithelium following their formation from stem cells in the basal portion of this neuroepithelium. Thus, the primary olfactory pathway is exquisitely suited to examine a role of B-50/GAP- 43 in neuronal migration, lifespan, and nerve fiber growth. We find that B-50/GAP-43 expression in adult olfactory neurons results in numerous primary olfactory axons with enlarged endings preferentially located at the rim of individual glomeruli. Furthermore, ectopic olfactory nerve fibers in between the juxtaglomerular neurons or in close approximation to blood vessels were frequently observed. This suggests that expression of B-50/GAP-43 in mature olfactory neurons alters their response to signals in the bulb. Other parameters examined, that is, migration and lifespan of olfactory neurons are normal in B-50/GAP-43 transgenic mice. These observations provide direct in vivo evidence for a role of B-50/GAP-43 in nerve fiber formation and in the determination of the morphology of axons.
DOI：
10.1016/0169-328x(90)90071-k
发表时间：
1990-01-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
YANKNER, BA;BENOWITZ, LI;NEVE, RL
通讯作者：
NEVE, RL