Danglot G, Régnier V, Fauvet D, Vassal G, Kujas M, Bernheim A
Cytogénétique et Génétique Oncologiques, CNRS URA 1158, Institut Gustave Roussy, Villejuif, France.
Hum Mol Genet. 1995 May;4(5):915-20. doi: 10.1093/hmg/4.5.915.
The neurofibromatosis 1 gene seems to play essential roles at several different stages of life. During embryogenesis, it is involved in cardiac development while in the adult, neurofibromin (the corresponding protein) is mainly expressed in the nervous system, and therein, essentially in neurons, non-myelinating Schwann cells and oligodendrocytes. In addition, the NF1 gene is considered a tumor suppressor gene, since mutations have been associated with the occurrence of benign and malignant tumors in neuralcrest-derived tissues. Using reverse transcription-polymerase chain reaction (RT-PCR) analyses with primers located in exons 7 and 13, we have identified evidence of alternative splicing in this region of the NF1 gene. Cloning and sequencing of cDNA allowed the characterization of an isoform bearing an extra 30 bp sequence between exons 9 and 10a, leading to the insertion of 10 amino acids between residues 420 and 421 of neurofibromin. The insertion is conserved in the mouse. Examination of the pattern of expression of this isoform demonstrated a high level of expression in the central nervous system and an absence of expression in all the other normal tissues tested including peripheral nervous tissues derived from the neural crest. Analysis of brain tumors indicated a reduced expression of the alternative exon in medulloblastomas and oligodendrogliomas. The results presented here are consistent with tissue-specific expression of this alternative exon which we propose to call exon 9br.
神经纤维瘤病1基因似乎在生命的几个不同阶段发挥着重要作用。在胚胎发生过程中，它参与心脏发育，而在成体中，神经纤维瘤蛋白（相应的蛋白质）主要在神经系统中表达，并且在其中，主要在神经元、非髓鞘施万细胞和少突胶质细胞中表达。此外，NF1基因被认为是一种肿瘤抑制基因，因为突变与神经嵴衍生组织中良性和恶性肿瘤的发生有关。使用位于外显子7和13的引物进行逆转录-聚合酶链反应（RT-PCR）分析，我们已经在NF1基因的这个区域鉴定出了可变剪接的证据。cDNA的克隆和测序使得能够鉴定出一种异构体，其在外显子9和10a之间带有一个额外的30 bp序列，导致在神经纤维瘤蛋白的420和421位残基之间插入10个氨基酸。该插入在小鼠中是保守的。对这种异构体表达模式的检测表明，它在中枢神经系统中高表达，而在所有其他测试的正常组织中均不表达，包括源自神经嵴的外周神经组织。脑肿瘤分析表明，在髓母细胞瘤和少突胶质细胞瘤中，可变外显子的表达降低。本文给出的结果与这种可变外显子的组织特异性表达一致，我们建议将其称为外显子9br。
