The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse
The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse
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DOI：
10.1093/hmg/6.11.1873
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发表时间：
1997-10-01
影响因子：
3.5
通讯作者：
Wevrick, R
中科院分区：
文献类型：
--
作者：
MacDonald, HR;Wevrick, R
人类染色体15 q11-q13含有仅从一个亲本等位基因印记和表达的基因，Prader-Willi综合征（PWS）是由于人类染色体15 q近端上的一个或多个父本表达基因的表达缺失，最常见的是缺失或母本单亲二体性。在PWS缺失区发现了几个候选基因和一个可能的印迹中心。我们报道了人类necdin编码基因（NDN）位于PWS缺失区的着丝粒部分，位于两个印迹基因ZNF 127和SNRPN之间。小鼠necdin是一种只在脑内分化的神经元中表达的核蛋白，Necdin被认为在小鼠神经系统发育过程中控制有丝分裂后神经元细胞生长的永久性停滞。此外，我们证明了Ndn的表达仅限于来自新生小鼠脑的RNA中的父系等位基因。NDN的表达在许多人体组织中被检测到，其中在脑和胎盘中的表达水平最高。NDN仅由父系遗传的等位基因在人成纤维细胞中表达，Necdin基因表达的缺失可能导致PWS个体的脑发育障碍。
Human chromosome 15q11-q13 contains genes that are imprinted and expressed from only one parental allele, Prader-Willi syndrome (PWS) is due to the loss of expression of one or more paternally expressed genes on proximal human chromosome 15q, most often by deletion or maternal uniparental disomy. Several candidate genes and a putative imprinting centre have been identified in the deletion region, We report that the human necdin-encoding gene (NDN) is within the centromeric portion of the PWS deletion region, between the two imprinted genes ZNF127 and SNRPN. Murine necdin is a nuclear protein expressed exclusively in differentiated neurons in the brain, Necdin is postulated to govern the permanent arrest of cell growth of post-mitotic neurons during murine nervous system development, We have localized the mouse locus Ndn encoding necdin to chromosome 7 in a region of conserved synteny with human chromosome 15q11-q13, by genetic mapping in an interspecific backcross panel. Furthermore, we demonstrate that expression of Ndn is limited to the paternal allele in RNA from newborn mouse brain, Expression of NDN is detected in many human tissues, with highest levels of expression in brain and placenta. NDN is expressed exclusively from the paternally inherited allele in human fibroblasts, Loss of necdin gene expression may contribute to the disorder of brain development in individuals with PWS.