Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders.
Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders.
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DOI：
10.1016/j.ydbio.2014.08.026
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发表时间：
2014-11-01
影响因子：
2.7
通讯作者：
Niswander, Lee A.
中科院分区：
文献类型：
--
作者：
Hanson, M. Gartz;Fregoso, Veronica L.;Vrana, Justin D.;Tucker, Chandra L.;Niswander, Lee A.
过氧化物酶体生物发生障碍(PBD)是一种常染色体隐性遗传病，以骨骼、眼睛和脑的异常为特征。尽管包括PEX10突变在内的一些PBD患者在出生时就可以观察到包括周围神经系统(PNS)缺陷在内的神经功能缺陷，但PNS缺陷的胚胎学基础尚不清楚。使用正向遗传筛查，我们确定了Pex10缺乏症的小鼠模型，该模型在胎儿发育期间表现出神经异常。纯合子Pex10突变小鼠胚胎表现出与PBD缺陷相关的生化异常。在胚胎发育后期，Pex10纯合子突变小鼠会逐渐失去活动能力，出生时就会变得发紫，不久后就会死亡。纯合子Pex10突变胎儿表现为轴突和突触完整性降低，横隔膜轴突过度伸展，雪旺细胞数量减少。我们的神经病理学、分子和电生理学研究为PBD模型中PNS缺陷的胚胎学基础提供了新的见解。我们的发现确定PEX10的功能，以及可能的其他PEX蛋白，是脊椎运动回路的重要组成部分。
Peroxisome biogenesis disorders (PBD) are autosomal recessive disorders in humans characterized by skeletal, eye and brain abnormalities. Despite the fact that neurological deficits, including peripheral nervous system (PNS) defects, can be observed at birth in some PBD patients including those with PEX10 mutations, the embryological basis of the PNS defects is unclear. Using a forward genetic screen, we identified a mouse model for Pex10 deficiency that exhibits neurological abnormalities during fetal development. Homozygous Pex10 mutant mouse embryos display biochemical abnormalities related to a PBD deficiency. During late embryogenesis, Pex10 homozygous mutant mice experience progressive loss of movement and at birth they become cyanotic and die shortly thereafter. Homozygous Pex10 mutant fetuses display decreased integrity of axons and synapses, over-extension of axons in the diaphragm and decreased Schwann cell numbers. Our neuropathological, molecular and electrophysiological studies provide new insights into the embryological basis of the PNS deficits in a PBD model. Our findings identify PEX10 function, and likely other PEX proteins, as an essential component of the spinal locomotor circuit.
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影响因子：
3.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.95.13.7485
发表时间：
1998-06-23
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