Giant axon formation in mice lacking Kell, XK, or Kell and XK: animal models of McLeod neuroacanthocytosis syndrome.
Giant axon formation in mice lacking Kell, XK, or Kell and XK: animal models of McLeod neuroacanthocytosis syndrome.
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缺乏凯尔、XK 或凯尔和 XK 的小鼠中巨轴突形成：麦克劳德神经棘红细胞增多症综合征的动物模型。
DOI：
10.1016/j.ajpath.2013.11.013
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Lee,Soohee
中科院分区：
文献类型：
--
作者：
Zhu,Xiang;Cho,Eun-Sook;Sha,Quan;Peng,Jianbin;Oksov,Yelena;Kam,SiokYuen;Ho,Mengfatt;Walker,RuthH;Lee,Soohee
McLeod neuroacanthocytosis syndrome (MLS) is a rare X-linked multisystem disease caused byXKgene mutations and characterized by hematological and neurological abnormalities. XK, a putative membrane transporter, is expressed ubiquitously and is covalently linked to Kell, an endothelin-3-converting enzyme (ECE-3). Absence of XK results in reduction of Kell at sites where both proteins are coexpressed. To elucidate the functional roles of XK, Kell, and the XK–Kell complex associated with pathogenesis in MLS, we studied the pathology of the spinal cord, anterior roots, sciatic nerve, and skeletal muscle from knockout mouse models, usingKel−/−,Xk−/−,Kel−/−Xk−/−, and wild-type mice aged 6 to 18 months. A striking finding was that giant axons were frequently associated with paranodal demyelination. The pathology suggests probable anterograde progression from the spinal cord to the sciatic nerve. The neuropathological abnormalities were found in all three genotypes, but were more marked in the double-knockoutKel−/−Xk−/−mice than in eitherKel−/−orXk−/−mice. Skeletal muscles fromXk−/−andKel−/−Xk−/−mice showed mild abnormalities, but those fromKel−/−mice were similar to the wild type. The more marked neuropathological abnormalities inKel−/−Xk−/−mice suggest a possible functional association between XK and Kell in nonerythroid tissues.
