Heterozygous Peripheral Myelin Protein 22-Deficient Mice Are Affected by a Progressive Demyelinating Tomaculous Neuropathy
Heterozygous Peripheral Myelin Protein 22-Deficient Mice Are Affected by a Progressive Demyelinating Tomaculous Neuropathy
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杂合外周髓磷脂蛋白 22 缺陷小鼠受到进行性脱髓鞘性肿瘤神经病的影响
DOI：
10.1523/jneurosci.17-12-04662.1997
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
U. Suter
中科院分区：
文献类型：
--
作者：
K. Adlkofer;R. Frei;D. Neuberg;J. Zielasek;K. Toyka;U. Suter
遗传性压力性麻痹神经病(HNPP)与17号染色体上含有外周髓鞘蛋白(PMP)基因PMP22的1.5兆碱基杂合性缺失有关。我们发现杂合的PMP22基因敲除小鼠只携带一个功能性PMP22等位基因，因此在遗传上接近于HNPP，表现出与HNPP神经中观察到的相似的形态和电生理特征。正如以前报道的，HNPP的病理特征-局灶性超髓鞘结构称为斑点，在年轻的PMP22+/0小鼠中逐渐发展。通过跟踪番茄在衰老过程中的命运，我们现在证明了这些突变动物也是研究HNPP疾病机制的有趣模型。在1岁的PMP22+/0小鼠中检测到细微的电生理异常，并出现大量异常肿胀和退化的毛囊。形成洋葱鳞茎的稀疏髓鞘轴突和多余的雪旺细胞也是反复脱髓鞘和再髓鞘形成的指纹。对单个被梳理的神经纤维进行的电子显微镜和光学显微镜的定量分析表明，绒毛是本质上不稳定的结构，容易退化；然而，PMP22+/0小鼠的形态和电生理异常的严重程度是不同的。这些综合发现使人联想到HNPP的疾病进展，并为一些HNPP患者在晚年发展成慢性运动和感觉神经病变提供了可能的解释，无论从形态还是临床标准来看，这种疾病都类似于Charcot-Marie-Tooth病的脱髓鞘形式。
Hereditary neuropathy with liability to pressure palsy (HNPP) is associated with a heterozygous 1.5 megabase deletion on chromosome 17 that includes the peripheral myelin protein (PMP) genePMP22. We show that heterozygous PMP22 knock-out mice, which carry only one functional pmp22 allele and thus genetically mimic HNPP closely, display similar morphological and electrophysiological features as observed in HNPP nerves. As reported previously, focal hypermyelinating structures called tomacula, the pathological hallmarks of HNPP, develop progressively in young PMP22+/0 mice. By following the fate of tomacula during aging, we demonstrate now that these mutant animals are also interesting models for examining HNPP disease mechanisms. Subtle electrophysiological abnormalities are detected in PMP22+/0mice >1 year old, and a significant number of abnormally swollen and degenerating tomacula are present. Thinly myelinated axons and supernumerary Schwann cells forming onion bulbs as fingerprints of repeated cycles of demyelination and remyelination are also encountered frequently. Quantitative analyses using electron microscopy on cross sections and light microscopy on single teased nerve fibers suggest that tomacula are intrinsically unstable structures that are prone to degeneration; however, the severity of morphological and electrophysiological abnormalities in PMP22+/0 mice is variable. These combined findings are reminiscent of the disease progression in HNPP and offer a possible explanation about why some HNPP patients develop a chronic motor and sensory neuropathy later in life that resembles demyelinating forms of Charcot-Marie-Tooth disease by both morphological and clinical criteria.
影响因子：
4.4
作者：
C. Ruegg;H. Y. Wu;F. Fagnoni;E. Engleman;R. Laus
通讯作者：
C. Ruegg;H. Y. Wu;F. Fagnoni;E. Engleman;R. Laus
髓磷脂蛋白由生长停滞特异性基因的同源物编码。
DOI：
10.1073/pnas.88.16.7195
发表时间：
1991
影响因子：
11.1
作者：
Welcher,AA;Suter,U;DeLeon,M;Snipes,GJ;Shooter,EM
通讯作者：
Shooter,EM
trembler-J 小鼠 22 kDa 外周髓磷脂蛋白的假定第一跨膜结构域中亮氨酸到脯氨酸的突变。
DOI：
10.1073/pnas.89.10.4382
发表时间：
1992
影响因子：
11.1
作者：
Suter,U;Moskow,JJ;Welcher,AA;Snipes,GJ;Kosaras,B;Sidman,RL;Buchberg,AM;Shooter,EM
通讯作者：
Shooter,EM