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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Knockout of the priori protein (PrP)-like Sprn gene does not produce embryonic lethality in combination with PrP~C-deficiency
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Knockout of the priori protein (PrP)-like Sprn gene does not produce embryonic lethality in combination with PrP~C-deficiency

机译:先验蛋白(PrP)样Sprn基因的敲除结合PrP〜C缺陷不会产生胚胎致死性

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摘要

The Sprn gene encodes Shadoo (Sho), a glycoprotein with biochemical properties similar to the unstructured, region of cellular prion protein (PrP~C). Sho has been considered a candidate for the hypothetical n protein that supplies a PrP~C-like function to maintain the viability of Prnp~(0/0) mice lacking the PrP~C protein. To understand these relationships more clearly we probed the cell biology of Sho and created knockout mice. Besides full-length and a "C1" C-terminal fragment, we describe a 6-kDa N-terminal Sho neuro-peptide, "N1," which is present in membrane-enriched subcellular fractions of wild-type mice. Sprn null alleles were produced that delete all protein coding sequences yet spare the Mtg1 gene transcription unit that overlaps the Sprn 3' UTR; the resulting mice bred to homozygosity were viable and fertile, although Sprn~(0/0) mice maintained in two genetic backgrounds weighed less than wild-type mice. Lack of Sho protein did not affect prion incubation time. Contrasting with lethality reported for knockdown of expression in Prnp~(0/0) embryos using lentiviruses targeted against the Sprn 3' UTR, we established that double-knockout mice deficient in both Sho and PrP~C are fertile and viable up to 690 d of age. Our data reduce the impetus for equating Sho with the notional n protein and are not readily reconciled with hypotheses wherein expression of PrP~C and Sho are both required for completion of embryogenesis. Alternatively, and in accord with some reports for PrP~C, we infer that Sho's activity will prove germane to the maintenance of neuronal viability in postnatal life.
机译:Sprn基因编码Shadoo(Sho),一种具有类似于细胞病毒蛋白(PrP〜C)非结构化区域的生化特性的糖蛋白。 Sho被认为是假设的n蛋白的候选者,该蛋白提供了PrP〜C样功能来维持缺乏PrP〜C蛋白的Prnp〜(0/0)小鼠的活力。为了更清楚地了解这些关系,我们研究了Sho的细胞生物学并创建了敲除小鼠。除了全长和一个“ C1” C端片段,我们描述了一个6-kDa N端Sho神经肽“ N1”,它存在于野生型小鼠的富含膜的亚细胞部分中。产生了Sprn无效等位基因,其删除了所有蛋白质编码序列,但保留了与Sprn 3'UTR重叠的Mtg1基因转录单位;尽管在两个遗传背景下维持的Sprn〜(0/0)小鼠的体重都比野生型小鼠轻,但它们产生的纯合子小鼠却是活的和肥沃的。缺乏Sho蛋白不会影响病毒的孵育时间。与报道的使用针对Sprn 3'UTR的慢病毒在Prnp〜(0/0)胚胎中敲低表达的致死率相反,我们确定Sho和PrP〜C均缺乏的双敲除小鼠可育并能存活至690 d年龄。我们的数据减少了用概念n蛋白等同于Sho的推动力,并且不容易与其中完成胚胎发生需要PrP〜C和Sho的表达的假说相吻合。另外,根据有关PrP〜C的报道,我们推断Sho的活动将证明与维持出生后神经元生存能力密切相关。

著录项

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  • 作者单位

    Centre for Prions and Protein Folding Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8;

    Centre for Prions and Protein Folding Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8;

    McLaughin Research Institute, Great Falls, MT 59405;

    McLaughin Research Institute, Great Falls, MT 59405;

    Centre for Prions and Protein Folding Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8;

    Centre for Prions and Protein Folding Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8;

    McLaughin Research Institute, Great Falls, MT 59405;

    Centre for Prions and Protein Folding Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8 Department of Biochemistry, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8 Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2M8;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    disease susceptibility; genetic redundancy; prion gene family;

    机译:疾病易感性基因冗余;ion病毒基因家族;

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