Transgenic systems in studying myelin gene expression - PubMed (original) (raw)

Review

Transgenic systems in studying myelin gene expression

K Ikenaka et al. Dev Neurosci. 1995.

Abstract

The myelin sheath is produced by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It is necessary to introduce DNA into these cells to study gene regulation and the functions of myelin proteins. Since these cells are labile to commonly used techniques to introduce DNA, a transgenic system must be used for these studies. Myelin basic protein (MBP) and myelin proteolipid protein (PLP) are both highly abundant in CNS myelin, but are also produced in Schwann cells. Various lengths (6.5 kb to 256 bp) of the promoter region of the (classic) MBP gene directed oligodendrocyte-specific expression of the reporter gene in transgenic mice, but no expression was seen in Schwann cells. Promoter regions of the PLP gene (4.2-2.4 kb) seem to contain all the information required for correct spatiotemporal expression, but the level of expression was low. The first intron of the PLP gene is a candidate for the location of the enhancer-like element. Studies on MBP mutant mice carrying wild-type MBP gene or cDNA clearly demonstrated that one function of MBP is to make myelin lamellae compact by fusing the cytoplasmic surfaces of oligodendrocytes into the form of major dense lines. However, functional analysis of PLP gene products using a similar strategy produced confusing results. The wild-type PLP gene introduced into jimpy mutant mice (one of the PLP mutants) did not complement the mutant phenotype. Moreover, overexpression of the PLP gene itself (in wild-type background) was shown to produce a phenotype similar to that of the mutants, including arrest in oligodendrocyte maturation and hypomyelination. Thus, PLP gene products play a fundamental role in oligodendrocyte maturation as well as in the stabilization of myelin structure, and its expression must be tightly regulated.

PubMed Disclaimer

Cited by

The evolution of lipophilin genes from invertebrates to tetrapods: DM-20 cannot replace proteolipid protein in CNS myelin.
Stecca B, Southwood CM, Gragerov A, Kelley KA, Friedrich VL Jr, Gow A. Stecca B, et al. J Neurosci. 2000 Jun 1;20(11):4002-10. doi: 10.1523/JNEUROSCI.20-11-04002.2000. J Neurosci. 2000. PMID: 10818135 Free PMC article.
On the occurrence of hypomyelination in a transgenic mouse model: a consequence of the myelin basic protein promoter?
Gaupp S, Arezzo J, Dutta DJ, John GR, Raine CS. Gaupp S, et al. J Neuropathol Exp Neurol. 2011 Dec;70(12):1138-50. doi: 10.1097/NEN.0b013e31823b188b. J Neuropathol Exp Neurol. 2011. PMID: 22082665 Free PMC article.
The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease.
Southwood CM, Garbern J, Jiang W, Gow A. Southwood CM, et al. Neuron. 2002 Nov 14;36(4):585-96. doi: 10.1016/s0896-6273(02)01045-0. Neuron. 2002. PMID: 12441049 Free PMC article.
Usefulness of a mouse myelin basic protein promoter for gene therapy of malignant glioma: myelin basic protein promoter is strongly active in human malignant glioma cells.
Miyao Y, Shimizu K, Tamura M, Akita H, Ikeda K, Mabuchi E, Kishima H, Hayakawa T, Ikenaka K. Miyao Y, et al. Jpn J Cancer Res. 1997 Jul;88(7):678-86. doi: 10.1111/j.1349-7006.1997.tb00436.x. Jpn J Cancer Res. 1997. PMID: 9310141 Free PMC article.
Genomic rearrangements resulting in PLP1 deletion occur by nonhomologous end joining and cause different dysmyelinating phenotypes in males and females.
Inoue K, Osaka H, Thurston VC, Clarke JT, Yoneyama A, Rosenbarker L, Bird TD, Hodes ME, Shaffer LG, Lupski JR. Inoue K, et al. Am J Hum Genet. 2002 Oct;71(4):838-53. doi: 10.1086/342728. Epub 2002 Sep 20. Am J Hum Genet. 2002. PMID: 12297985 Free PMC article.

Transgenic systems in studying myelin gene expression - PubMed (original) (raw)