Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice
Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice
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DOI：
10.1038/ng.2723
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发表时间：
2013-09-01
期刊：
影响因子：
30.8
通讯作者：
Oliveira, Joao R. M.
中科院分区：
文献类型：
--
作者：
Keller, Annika;Westenberger, Ana;Oliveira, Joao R. M.
基底节钙化是一种常见的偶然发现，有时作为常染色体显性遗传（特发性基底节钙化（IBGC））。最近，编码血小板衍生生长因子受体β（PDGF-R β）的PDGFRB基因突变与IBGC有关。在这里，我们确定了六个不同祖先的家族，在编码PDGF-B的基因中存在无义和错义突变，PDGF-B是PDGF-R β的主要配体。我们还发现，携带亚型Pdgfb等位基因的小鼠出现了与年龄相关的脑钙化。这些钙沉积的发生取决于内皮细胞PDGF-B的丢失，并与周细胞和血脑屏障缺陷的程度相关。因此，我们的数据显示了小鼠中Pdgfb突变和脑钙化之间以及人类中PDGFB突变和IBGC之间的明确联系。
Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait ( idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor beta (PDGF-R beta) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-R beta. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.