PMID: 7538670May 9, 1995Paper

Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein

Proceedings of the National Academy of Sciences of the United States of America
A M SchneiderK-A Nave

Abstract

Mutations in genes encoding membrane proteins have been associated with cell death of unknown cause from invertebrate development to human degenerative diseases. A point mutation in the gene for myelin proteolipid protein (PLP) underlies oligodendrocyte death and dysmyelination in jimpy mice, an accurate model for Pelizaeus-Merzbacher disease. To distinguish the loss of PLP function from other effects of the misfolded protein, we took advantage of the X chromosomal linkage of the gene and have complemented jimpy with a wild-type PLP transgene. In this artificial heterozygous situation, the jimpy mutation emerged as genetically dominant. At the cellular level oligodendrocytes showed little increase in survival although endogenous PLP gene and autosomal transgene were truly coexpressed. In surviving oligodendrocytes, wild-type PLP was functional and immunodetectable in myelin. Moreover, compacted myelin sheaths regained their normal periodicity. This strongly suggests that, despite the presence of functional wild-type PLP, misfolded jimpy PLP is by itself the primary cause of abnormal oligodendrocyte death.

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Citations

Jan 7, 1998·Journal of Neuroscience Research·S Forss-PetterK A Nave
Oct 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·I R Griffiths
Oct 15, 1995·Microscopy Research and Technique·K F LunnI D Duncan
May 26, 1998·Brain Research. Brain Research Reviews·J M VelaB Castellano
May 20, 2008·Expert Reviews in Molecular Medicine·Karen J Woodward
Jun 20, 1998·Neuropathology and Applied Neurobiology·C Huxley
Dec 10, 1999·Annals of the New York Academy of Sciences·J Y GarbernJ Kamholz
Jul 1, 1996·Brain Pathology·M Bradl, C Linington
Sep 6, 2001·Pharmacogenomics·K Woodward, S Malcolm
Nov 6, 1998·Brain Pathology·H WernerK A Nave
Jun 12, 2014·Cellular Oncology (Dordrecht)·Cyndia CharfiEric Rassart
Feb 23, 2010·Journal of Neuroscience Research·Jennifer A BarrieMark McLaughlin
May 18, 2013·Toxicology and Applied Pharmacology·Nagendra Kumar RaiSanghamitra Bandyopadhyay
Dec 26, 2001·Molecular and Cellular Neurosciences·H WernerK A Nave
Mar 1, 2015·Biochimica Et Biophysica Acta·Gesine Saher, Sina Kristin Stumpf
Apr 1, 2014·American Journal of Human Genetics·Thomas PrukopMichael W Sereda
Jul 22, 1998·Microscopy Research and Technique·I GriffithsK A Nave
May 6, 1999·Nature Medicine·A SchneiderM Schwaninger
Jan 20, 2017·Frontiers in Molecular Neuroscience·Vera G VolpiMaurizio D'Antonio
Oct 1, 1999·Annals of the New York Academy of Sciences·James Y GarbernJohn Kamholz

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