Peripheral nerve dysmyelination due to P0 glycoprotein overexpression is dose-dependent

Angelo Quattrini, Maria Laura Feltri, Stefano Previtali, Marina Fasolini, Albee Messing, Lawrence Wrabetz

Research output: Contribution to journalArticle

Abstract

We have previously shown that increased dosage of the mouse protein zero gene (Mpz) causes a dysmyelinating neuropathy in transgenic (Tg80) mice. To ask whether the dysmyelination is dose dependent, we inbred one of the Tg80 lines and compared the resulting phenotype in homozygous and heterozygous mice. Whereas heterozygous mice (30% overexpression) have only transient peripheral nerve hypomyelination at two weeks after birth and normal myelin at four weeks after birth, homozygous mice demonstrated more severely hypomyelinated nerves. In the latter, many Schwann cells had achieved a one-to-one relationship with large axons but formed no myelin at four weeks after birth. Expression analysis confirmed a doubling of Mpz overexpression in the sciatic nerves of the homozygous mice. Thus, a threshold exists for Mpz overexpression, above which dysmyelination results. These data have important implications for replacement therapy in Charcot-Marie-Tooth 1B neuropathies due to loss of P0 function.

Original languageEnglish
Pages (from-to)294-301
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume883
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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