Genetic Deletion of Cadm4 Results in Myelin Abnormalities Resembling Charcot-Marie-Tooth Neuropathy

Neev Golan, Elena Kartvelishvily, Ivo Spiegel, Daniela Salomon, Helena Sabanay, Katya Rechav, Anya Vainshtein, Shahar Frechter, Galia Maik-Rachline, Eisenbach, Yael Eshed Eisenbach, Takashi Momoi, Elior Peles

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

The interaction between myelinating Schwann cells and the axons they ensheath is mediated by cell adhesion molecules of the Cadm/Necl/SynCAM family. This family consists of four members: Cadm4/Necl4 and Cadm1/Necl2 are found in both glia and axons, whereas Cadm2/Necl3 and Cadm3/Necl1 are expressed by sensory and motor neurons. By generating mice lacking each of the Cadm genes, we now demonstrate that Cadm4 plays a role in the establishment of the myelin unit in the peripheral nervous system. Mice lacking Cadm4 (PGK-Cre/Cadm4(fl/fl)), but not Cadm1, Cadm2, or Cadm3, develop focal hypermyelination characterized by tomacula and myelin outfoldings, which are the hallmark of several Charcot-Marie-Tooth neuropathies. The absence of Cadm4 also resulted in abnormal axon-glial contact and redistribution of ion channels along the axon. These neuropathological features were also found in transgenic mice expressing a dominant-negative mutant of Cadm4 lacking its cytoplasmic domain in myelinating glia Tg(mbp-Cadm4dCT), as well as in mice lacking Cadm4 specifically in Schwann cells (DHH-Cre/Cadm4(fl/fl)). Consistent with these abnormalities, both PGK-Cre/Cadm4(fl/fl) and Tg(mbp-Cadm4dCT) mice exhibit impaired motor function and slower nerve conduction velocity. These findings indicate that Cadm4 regulates the growth of the myelin unit and the organization of the underlying axonal membrane.
اللغة الأصليةالإنجليزيّة
الصفحات (من إلى)10950-10961
عدد الصفحات12
دوريةJournal of Neuroscience
مستوى الصوت33
رقم الإصدار27
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - يوليو 2013

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