Premature arrest of myelin formation in transgenic mice with increased proteolipid protein gene dosage

doi:10.1016/0896-6273(94)90214-3

Neuron

Volume 12, Issue 3, March 1994, Pages 583-595

https://doi.org/10.1016/0896-6273(94)90214-3 Get rights and content

Summary

Proteolipid protein (PLP) is an integral membrane protein of CNS myelin. Mutations of the X chromosome-linked PLP gene cause glial cell death and myelin deficiency in jimpy mice and other neurological mutants. As part of an attempt to rescue these mutants by transgenic complementation, we generated normal mouse lines expressing autosomal copies of the entire wild-type PLP gene. Surprisingly, increase of the PLP gene dosage in nonmutant mice with only 2-fold transcriptional overex-pression results in a novel phenotype characterized by severe hypomyelination and astrocytosis, seizures, and premature death. This demonstrates that precise control of the PLP gene is a critical determinant of terminal oligodendrocyte differentiation. Dysmyelination of PLP transgenic mice provides experimental evidence that Pelizaeus-Merzbacher disease, previously associated with a partial duplication of the human X chromosome, can be caused by doubling of the PLP gene dosage.

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Neuron

Premature arrest of myelin formation in transgenic mice with increased proteolipid protein gene dosage

Summary

Cell

Anal. Biochem.

Cell

Trends Genet.

Neuron

J. Mol. Biol.

Neuron

Neuron

Cell

Cell

Cell

Neuron

Cell

Neuron

Brain Res.

Trends Neurosci.

Neuron

Cell

Neuron

A single human keratin 18 gene is expressed in diverse epithelial cells of transgenic mice

J. Cell Biol.

Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic β cells

Nature

Myelin-deficient rat: a point mutation in exon 3 (A→C, Thr75→Pro) of the myelin proteo-lipid protein causes dysmyelination and oligodendrocyte death

EMBO J.

An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region

Hum. Genet.

Molecular analysis of male-viable deletions and duplications allows ordering of 52 DNA probes on proximal Xq

Am. J. Hum. Genet.

p1B15: a cDNA clone of the rat mRNA encoding cyclophilin

DNA

Ultrastructure of the central nervous system in a myelin deficient rat

J. Neurocytol.

Individual exons encode the integral membrane domains of human myelin proteolipid protein

Proc. Natl. Acad. Sci. USA

Rumpshaker: an X-linked mutation causing hypomyelination: developmental differences in myelination and glial cells between the optic nerve and spinal cord

Glia

Conservative amino acid substitution in the myelin proteolipid protein of jimpymsd mice

J. Neurosci.

Conservative amino acid substitution in the myelin proteolipid protein of jimpy^msd mice