Altered molecular architecture of peripheral nerves in mice lacking the peripheral myelin protein 22 or connexin32

Peripheral nerves of mutant mice deficient for peripheral myelin protein 22 (PMP22) or connexin32 (Cx32) display similar pathologies as observed in he reditary human peripheral neuropathies, Mice lacking PMP22 develop focal hy permyelination followed by myelin degeneration and axonal atrophy, Cx32-def icient mice form normal myelin initially but develop demyelination and remy elination at older ages, We have examined the lack of PMP22 or Cx32 on the distribution of other components of the myelin sheath including myelin basi c protein (MBP), E-cadherin, and myelin-associated glycoprotein (MAG), as w ell as the delayed rectifying potassium channel Kv1.1 as an intrinsic membr ane protein of axons, In peripheral nerves of mild-type mice, Kv1.1 is pres ent as a pair of juxtaparanodal clusters and a focal line extending longitu dinally into the internode, branching parallel and adjacent to Schmidt-Lant erman incisures, Myelinated peripheral nerve fibers of 3-week-old PMP22(0/0 ) mice show tomacula and abnormally short internodes of variable lengths wi th minor effects on the localization of E-cadherin and Kv1.1, In older PMP2 2(0/0) mice, hypomyelinated fibers contain supernumerary Schwann cells and loose focally restricted E-cadherin and Kv1.1 expression, In contrast, remy elinated fibers in adult Cx32(0/0) mice exhibit a correct localization of t hese marker proteins, except that juxtaparanodal Kv1.1 clusters are aligned in abnormally short intervals of regular distances accompanied by an incre ased number of Schwann cells, Thus, different degrees of demyelination and remyelination in demyelinating mouse models have variable effects on the co nfinement of specific proteins to structural and functional internodal doma ins. (C) 1999 Wiley-Liss, Inc.