The peripheral myelin gene PMP–22/GAS–3 is duplicated in Charcot–Marie–Tooth disease type 1A

Valentijn, Linda J.; Bolhuis, P. A.; Zorn, I.; Hoogendijk, Jessica E.; Bosch, Nina; Hensels, G. W.; Stanton, Vincent P.; Housman, David E.; Fischbeck, Kenneth H.; Ross, David A.; Nicholson, Garth A.; Meershoek, Eric J.; Dauwerse, Hans G.; Ommen, G.J.B. van; Baas, Frank

doi:10.1038/ng0692-166

Cited by 296 publications

(126 citation statements)

References 21 publications

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“…CL-20 is localized on chromosome 12 while PMP22 has been mapped at 17p12-13 (27,(31)(32)(33). Genetic alterations in the expression of PMP22 have been implicated in several neuropathies specific for the peripheral nervous system.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Novel Squamous Cell-associated Gene Related to PMP22

Marvin¹,

Fujimoto²,

Jetten³

1995

Journal of Biological Chemistry

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In this study, we identify and characterize a novel gene, CL-20, that encodes a 17.8-kDa protein with sequence and structural similarity to the growth arrestspecific gene gas3/peripheral myelin protein gene PMP22. The CL-20 protein exhibits a 43% identity with PMP22. The positions of the four lipophilic domains and the N-glycosylation site of PMP22 are conserved in CL-20, suggesting that it also is an integral membrane glycoprotein. The CL-20 gene is located on human chromosome 12 rather than 17 and encodes a 2.8-kilobase mRNA instead of 1.7-kilobase mRNA. These observations indicate that the CL-20 gene is related to but distinct from PMP22. In contrast to PMP22, CL-20 mRNA and protein are induced during squamous differentiation of rabbit tracheal epithelial cells in vitro, and Northern blot analysis and in situ hybridization demonstrated that CL-20 mRNA is most abundant in squamous epithelia. These results indicate that the high expression of CL-20 is closely correlated with squamous differentiation. The differences in tissue-specific expression and regulation between CL-20 and PMP22 suggest different roles for these two proteins. Retinoids, which inhibit squamous differentiation, repress the induction of CL-20. The retinoic acid receptor-selective retinoid SRI-6751-84 is the most effective in suppressing CL-20, suggesting that the activation of the retinoic acid receptor signaling pathway is important in this suppression.Squamous differentiation can be observed in many tissues including the trachea, bronchus, and skin. The lining of the trachea and bronchi normally consists of a pseudostratified columnar epithelium (1). During vitamin A deficiency or after toxic assault or mechanical injury (2-4), regions of the mucociliary epithelium are replaced by a stratified squamous epithelium. Tracheobronchial epithelial cells also undergo squamous differentiation when cultured in medium deficient in retinoids (5-7). In many respects, squamous differentiation in the tracheobronchial epithelial cells resembles differentiation in epidermal keratinocytes and other squamous differentiating tissues (8). The histologically distinct layers constituting the squamous epithelium (8) exhibit distinctive patterns of expression of specific genes and are evidence that squamous differentiation is a multistage process (5, 9, 10). Early in this differentiation process, cells irreversibly lose their proliferative potential and down-regulate the expression of the cell cycleassociated genes cdc2 and E2F-1 (11, 12). This is followed by the expression of squamous-specific genes such as transglutaminase type I (7, 13-15), the cross-linked envelope precursors involucrin, loricrin, and cornifin (16 -19), cholesterol sulfotransferase (20), and specific keratins (9, 21). These genes have been cloned and are shown to be regulated by a variety of agents including retinoids, which suppress the expression of squamous-specific genes (7-21).In this study, we describe the isolation and characterization of a cDNA CL-20 that was isolated from a cDNA libra...

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Novel Squamous Cell-associated Gene Related to PMP22

Marvin¹,

Fujimoto²,

Jetten³

1995

Journal of Biological Chemistry

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“…Specifically, the hereditary neuropathy with liability to pressure palsies (HNPP) is caused by a deletion of the PMP22 gene, 11,12 while the demyelinating hereditary motor sensory neuropathy Charcot-Marie-Tooth disease type 1A (CMT1A) is due to a heterozygous duplication of the same DNA segment. 13 In rare cases, CMT1A can also be caused by point mutations in the PMP22 gene, and in mice, similar mutations are associated with the Trembler and Trembler-J phenotype. [14][15][16] In sum, these data suggest that both elevated and reduced levels of PMP22 can cause apoptosis and tissue degeneration.…”

Section: Introductionmentioning

confidence: 99%

Perp is required for tissue-specific cell survival during zebrafish development

2004

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The tumor suppressor p53 has two alternative effects, causing either cell cycle arrest or apoptosis. These different effects are supposed to be mediated by the transcriptional activation of different target genes. perp, encoding a transmembrane protein of the Pmp22 family, is a transcriptional p53 target exclusively upregulated in apoptotic cells. However, its role during normal development had remained largely unclear. Here, we report the isolation and characterization of a zebrafish perp homolog. Upon overexpression in early zebrafish embryos, perp induces apoptosis. In addition, it contributes to p53-dependent and UVinduced cell death. However, during normal zebrafish development, perp displays a p53-independent and spatially restricted expression in specific cell types and tissues. Antisensemediated loss of Perp function leads to increased apoptosis in perp-expressing cells of the developing skin and notochord. We conclude that, in contrast to its proapoptotic function in stressed cells, Perp plays an antiapoptotic role during normal zebrafish development to regulate tissue-specific cell survival. Cell Death and Differentiation (2005) Keywords: perp; p53; pmp22; apoptosis; cell survival; zebrafish; development Abbreviations: AO, acridine orange; BrdU, 5 0 Bromo-2 0 -desoxyuridine; DNp63, amino-terminally truncated isoform of p63; EST, expressed sequence tag; EVL, enveloping layer; hpf, hours postfertilization; mdm2, mouse double minute 2; MO, morpholino oligonucleotide; RT-PCR, polymerase chain reaction after reverse transcription of RNA; SDS-PAGE, sodiumdodecylsulfate polyacrylamide gel electrophoresis; TAp73, transactivating N-terminally full-length isoform of p73; TUNEL, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling; UV, ultraviolet; 4 mm, four mismatch control

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“…Point mutations in the human PMP22 gene have also been identified in some Charcot-Marie-Tooth disease type 1A (C MT1A) families (Valentijn et al, 1992b;Roa et al, 1993a,b) and in the clinically more severe hypertrophic neuropathy Dejerine -Sottas syndrome (Roa et al, 1993c). However, in most C MT1A patients the PMP22 gene is duplicated (Matsunami et al, 1992;Patel et al, 1992;Timmerman et al, 1992;Valentijn et al, 1992a). Furthermore, a heterozygous deletion of the same chromosomal region that is duplicated in CMT1A families has been detected in patients with hereditary neuropathy with liability to pressure palsies (HN PP) (Chance et al, 1993(Chance et al, , 1994.…”

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confidence: 99%

Neurons Promote the Translocation of Peripheral Myelin Protein 22 into Myelin

et al. 1997

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Schwann cells express low levels of myelin proteins in the absence of neurons. When Schwann cells and neurons are cultured together the production of myelin proteins is elevated, and myelin is formed. For peripheral myelin protein 22 (PMP22), the exact amount of protein produced is critical, because peripheral neuropathies result from its underexpression or overexpression. In this study we examined the effect of neurons on Schwann cell PMP22 production in culture and in peripheral nerve using metabolic labeling and pulse-chase studies as well as immunocytochemistry. Most of the newly synthesized PMP22 in Schwann cells is rapidly degraded in the endoplasmic reticulum. Only a small proportion of the total PMP22 acquires complex glycosylation and accumulates in the Golgi compartment. This material is translocated to the Schwann cell membrane in detectable amounts only when axonal contact and myelination occur. Myelination does not, however, alter the rapid turnover of PMP22 in Schwann cells. PMP22 may therefore be a unique myelin protein in that axonal contact promotes its insertion into the Schwann cell membrane and myelin without altering its rapid turnover rate within the cell.

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The peripheral myelin gene PMP–22/GAS–3 is duplicated in Charcot–Marie–Tooth disease type 1A

Cited by 296 publications

References 21 publications

Identification and Characterization of a Novel Squamous Cell-associated Gene Related to PMP22

Identification and Characterization of a Novel Squamous Cell-associated Gene Related to PMP22

Perp is required for tissue-specific cell survival during zebrafish development

Neurons Promote the Translocation of Peripheral Myelin Protein 22 into Myelin

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