• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity
【24h】

A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity

机译：Bardet-Biedl综合征1 M390R突变的敲入小鼠模型具有纤毛缺陷，脑室肥大，视网膜病变和肥胖

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder that results in retinal degeneration, obesity, cognitive impairment, polydactyly, renal abnormalities, and hypogenitalism. Of the 12 known BBS genes, BBS1 is the most commonly mutated, and a single missense mutation (M390R) accounts for ≈ 80% of BBS1 cases. To gain insight into the function of BBS1, we generated a Bbs1~(M390R/M390R) knockin mouse model. Mice homozygous for the M390R mutation recapitulated aspects of the human phenotype, including retinal degeneration, male infertility, and obesity. The obese mutant mice were hyperphagic and hyperleptinemic and exhibited reduced locomotor activity but no elevation in mean arterial blood pressure. Morphological evaluation of Bbs1 mutant brain neuroanatomy revealed ventriculomegaly of the lateral and third ventricles, thinning of the cerebral cortex, and reduced volume of the corpus striatum and hippocampus. Similar abnormalities were also observed in the brains of Bbs2~(-/-), Bbs4~(-/-), and Bbs6~(-/-) mice, establishing these neuroanatomical defects as a previously undescribed BBS mouse model phenotype. Ultrastruc-tural examination of the ependymal cell cilia that line the enlarged third ventricle of the Bbs1 mutant brains showed that, whereas the 9 + 2 arrangement of axonemal microtubules was intact, elongated cilia and cilia with abnormally swollen distal ends were present. Together with data from transmission electron microscopy analysis of photoreceptor cell connecting cilia, the Bbs1 M390R mutation does not affect axonemal structure, but it may play a role in the regulation of cilia assembly and/or function.
机译：Bardet-Biedl综合征（BBS）是一种遗传异质性疾病，可导致视网膜变性，肥胖，认知障碍，多指畸形，肾脏异常和性欲低下。在12个已知的BBS基因中，BBS1是最常见的突变，而单个错义突变（M390R）占BBS1病例的约80％。为了深入了解BBS1的功能，我们生成了Bbs1〜（M390R / M390R）敲入小鼠模型。 M390R突变的纯合小鼠概括了人类表型的各个方面，包括视网膜变性，男性不育和肥胖。肥胖的突变小鼠是高食性和高脂血症的，并且运动能力降低，但平均动脉压没有升高。 Bbs1突变型大脑神经解剖学的形态学评估显示侧脑室和第三脑室大，大脑皮层变薄，纹状体和海马体体积减少。在Bbs2〜（-/-），Bbs4〜（-/-）和Bbs6〜（-/-）小鼠的大脑中也观察到了类似的异常，将这些神经解剖缺陷确立为先前未描述的BBS小鼠模型表型。对沿Bbs1突变型脑的扩大的第三脑室排列的室间隔细胞纤毛的超微结构检查显示，尽管轴突微管的9 + 2排列完好无损，但纤毛和纤毛存在远端异常膨大的现象。 Bbs1 M390R突变与来自连接纤毛的感光细胞的透射电镜分析数据一起，不影响轴突结构，但可能在调节纤毛组装和/或功能中起作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号