REDUCED CYCLIC-AMP PRODUCTION IN FRAGILE-X SYNDROME - CYTOGENETIC AND MOLECULAR CORRELATIONS
REDUCED CYCLIC-AMP PRODUCTION IN FRAGILE-X SYNDROME - CYTOGENETIC AND MOLECULAR CORRELATIONS
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DOI：
10.1203/00006450-199511000-00002
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发表时间：
1995-11-01
影响因子：
3.6
通讯作者：
CIURLIONIS, R
中科院分区：
文献类型：
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作者：
BERRYKRAVIS, E;HICAR, M;CIURLIONIS, R
cAMP级联是一种细胞内信号转导系统，被认为对神经元调节和信息储存很重要。脆性X综合征患者血小板中cAMP生成减少在本研究中，我们检测了cAMP代谢，Xq27.3脆性位点百分比，扩增突变的大小在脆性X智力低下-1基因（FMR-1），和FMR-1 mRNA水平在21个淋巴母细胞系（LCL）从脆性X患者。与对照组（n = 20）相比，当细胞在前列腺素E（1）（74%，p < 0.02）和毛喉素（64%，p < 0.1）中测定时，脆性X LCL的cAMP产生减少，尽管仅在前列腺素E（1）中差异具有统计学意义。FMR-1扩增突变的长度与cAMP产生的测量值相关，而cAMP产生与受体活化无关（未刺激和毛喉素刺激的cAMP产生分别为r =-0.53，p = 0.02和r =-0.48，p = 0.03）。在脆性X LCL中，脆性位点百分比与cAMP产生的任何测量均不相关。Au脆性X LCL显示不存在FMR-1。mRNA。这些数据表明，在脆性X组织中减少的cAMP产生可能与脆性X扩增突变有关，这是由于突变对FMR-1表达或对FMR-1下游其他基因转录的影响。
The cAMP cascade is an intracellular signal transduction system thought to be important for neuronal regulation and information storage. cAMP production is reduced in platelets from patients with fragile X syndrome. In the present study we assayed cAMP metabolism, Xq27.3 fragile site percentages, size of amplification mutation in fragile X mental retardation-1 gene (FMR-1), and FMR-1 mRNA levels in 21 lymphoblastoid cell lines (LCL) from fragile X patients. cAMP production was diminished in fragile X LCL relative to controls (n = 20) when cells were assayed in prostaglandin E(1) (74%, p < 0.02) and in forskolin (64%, p < 0.1) although the difference was statistically significant only in prostaglandin E(1). The length of the FMR-1 amplification mutation correlated with measures of cAMP production which were unassociated with receptor activation (r = -0.53, p = 0.02, and r = -0.48, p = 0.03, for unstimulated and forskolin-stimulated cAMP production, respectively). Tn fragile X LCL, fragile site percentages did not correlate with any measure of cAMP production. AU fragile X LCL showed absence of FMR-1. mRNA. These data suggest that diminished cAMP production in fragile X tissues may be linked to the fragile X amplification mutation, either as a result of influences of the mutation on FMR-1 expression or on transcription of other genes downstream from FMR-1.