PQBP‐1 is expressed predominantly in the central nervous system during development
PQBP‐1 is expressed predominantly in the central nervous system during development
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DOI：
10.1111/j.1460-9568.2005.04339.x
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发表时间：
2005-09
影响因子：
3.4
通讯作者：
Y. Qi;M. Hoshino;Y. Wada;S. Marubuchi;N. Yoshimura;I. Kanazawa;K. Shinomiya;H. Okazawa
中科院分区：
文献类型：
--
作者：
Y. Qi;M. Hoshino;Y. Wada;S. Marubuchi;N. Yoshimura;I. Kanazawa;K. Shinomiya;H. Okazawa
PQBP‐1（聚谷氨酰胺结合蛋白‐1）的突变最近被证明可导致人类智力迟钝并伴有小头畸形。作为了解这种发育异常的分子基础的第一步，我们通过原位杂交、免疫组织化学和Western blot分析了PQBP‐1的发育表达。尽管Northern blot分析显示PQBP - 1 mRNA在成年小鼠的多个器官中表达，但我们目前的研究结果显示PQBP - 1 mRNA和蛋白主要表达在胚胎和新生小鼠的中枢神经系统（CNS）中。PQBP - 1的平均表达水平在出生前后达到峰值，并在成年后下调。此外，出生后中枢神经系统的表达模式发生了显著变化。大脑皮层中的PQBP - 1 mRNA在胚胎时期较高，但在出生后迅速下降。PQBP‐1 mRNA在出生后第1天（P1）至5天的小脑内、外颗粒细胞层中表达增加。此外，从P5到成年，发生神经发生的室下区表达量很高。总的来说，这些发现表明PQBP‐1可能参与神经元的增殖和/或成熟。这些观点可能与PQBP‐1相关的人类智力迟钝中所报道的大脑结构生长不足有关。
Mutations of PQBP‐1 (polyglutamine binding protein‐1) have been shown recently to cause human mental retardation accompanied by microcephaly at a high frequency. As a first step towards understanding the molecular basis of this developmental anomaly, we analysed developmental expression of PQBP‐1 by in situ hybridization, immunohistochemsitry and Western blot analysis. Although it had been shown by Northern blot analysis that PQBP‐1 mRNA is expressed in multiple organs in adult mice, our present results revealed that PQBP‐1 mRNA and protein are dominantly expressed in the central nervous system (CNS) in embryos and in newborn mice. The mean expression level of PQBP‐1 reaches a peak around birth and is down‐regulated in adulthood. Furthermore, the expression pattern in the CNS changes remarkably following birth. PQBP‐1 mRNA in the cerebral cortex is high in embryos but it rapidly decreases after birth. PQBP‐1 mRNA increases in external and internal granular cell layers of the cerebellum from postnatal day 1 (P1) to P5. In addition, expression in the subventricular zone, where neurogenesis occurs, was high from P5 to adulthood. Collectively, these findings suggest that PQBP‐1 might be involved in neuronal proliferation and/or maturation. These ideas may be relevant to the insufficient growth of brain structure reported in PQBP‐1‐linked human mental retardation.