Reduced PLP1 expression in induced pluripotent stem cells derived from a Pelizaeus-Merzbacher disease patient with a partial PLP1 duplication.
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder characterized by dysmyelination of the central nervous system (CNS). We identified a rare partial duplication of the proteolipid protein 1 gene (PLP1) in a patient with PMD. To assess the underlying effect of this duplication, we examined PLP1 expression in induced pluripotent stem (iPS) cells generated from the patient's fibroblasts. Disease-specific iPS cells were generated from skin fibroblasts obtained from the indicated PMD patient and two other PMD patients having a 637-kb chromosomal duplication including entire PLP1 and a novel missense mutation (W212C) of PLP1, by transfections of OCT3/4, C-MYC, KLF4 and SOX2 using retro-virus vectors. PLP1 expressions in the generated iPS cells were examined by northern blot analysis. Although PLP1 expression was confirmed in iPS cells generated from two patients with the entire PLP1 duplication and the missense mutation of PLP1, iPS cells generated from the patient with the partial PLP1 duplication manifesting a milder form of PMD showed null expression. This indicated that the underlying effect of the partial PLP1 duplication identified in this study was different from other PLP1 alterations including a typical duplication and a missense mutation.
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan.
Keiko
K
Shimojima
Takahito
T
Inoue
Yuki
Y
Imai
Yasuhiro
Y
Arai
Yuta
Y
Komoike
Midori
M
Sugawara
Takako
T
Fujita
Hiroshi
H
Ideguchi
Sawa
S
Yasumoto
Hitoshi
H
Kanno
Shinichi
S
Hirose
Toshiyuki
T
Yamamoto
D000293:Adolescent; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D045744:Cell Line, Tumor; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D005260:Female; D020440:Gene Duplication; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics* / Q000378:metabolism; D020371:Pelizaeus-Merzbacher Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human