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Peripheral Nerve Dysmyelination Due to P 0 Glycoprotein Overexpression Is Dose‐Dependent
Author(s) -
QUATTRINI ANGELO,
FELTRI MARIA LAURA,
PREVITALI STEFANO,
FASOLINI MARINA,
MESSING ALBEE,
WRABETZ LAWRENCE
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08591.x
Subject(s) - myelin , sciatic nerve , transgene , peripheral neuropathy , peripheral , genetically modified mouse , phenotype , peripheral nerve , myelin sheath , schwann cell , ratón , biology , endocrinology , medicine , pathology , gene , microbiology and biotechnology , anatomy , genetics , central nervous system , diabetes mellitus
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 P 0 function.