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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Mutations of GADD45G in rabbits cause cleft lip by the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT)
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Mutations of GADD45G in rabbits cause cleft lip by the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT)

机译：兔子的突变引起唇缘，扩散，细胞凋亡和上皮间过渡（EMT）

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摘要

The cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects in humans. Genome-wide association studies (GWAS) have been widely used for identifying candidate genes, and different genes or chromosomal regions have shown strong evidence for the presence of causal genes in CL/P. To date, two independent GWAS have identified GADD45G as influencing risk for CL/P. However, there is no animal model evidence about GADD45G related to CL/P. Here, we reported the generation of a novel GADD45G mutated rabbit model by CRISPR/Cas9 and CRISPR,based BE4-Gam systems. The homozygous (GADD45G(-/-)) while not heterozygous (GADD45G(+/-)) pups died after birth due to severe craniofacial defects of unilateral or bilateral cleft lip (CL). Moreover, the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were also determined in the medial and lateral nasal processes (MNP and LNP) of the embryonic day 13 (E13) GADD45G(-/-) rabbits, which compared with the normal wild type (WT) rabbits. Thus, our study confirmed for the first time that loss of GADD45G lead to CL at the animal level and provided new insights into the crucial role of GADD45G for upper lip formation and fusion.
机译：具有或没有腭裂（Cl / P）的唇裂是人类最常见的先天性缺陷之一。基因组 - 范围的协会研究（GWAs）已广泛用于鉴定候选基因，不同的基因或染色体区已经显示出CL / P中存在因果基因的有力证据。迄今为止，两个独立的GWA已将GADD45G识别为影响CL / P的风险。但是，没有动物模型证据关于与Cl / p相关的Gadd45g。在这里，我们报告了通过CRISPR / CAS9和CRISPR的BE4-GAM系统生成新的Gadd45G突变兔模型。纯合（gadd45g（ - / - ）），而不是杂合（Gadd45g（+/-））由于单侧或双侧裂隙唇（Cl）的严重颅面缺陷而在出生后死亡。此外，还在胚胎第13（E13）GADD45G（ - / - ）兔的内侧和横向鼻方法（MNP和LNP）中测定增殖，细胞凋亡和上皮间转化（EMT）的紊乱，与...相比正常的野生型（WT）兔。因此，我们的研究证实了在动物水平的第一次将GADD45g导致CL导致CL，并为上唇形成和融合的GADD45G的关键作用提供了新的见解。

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  • 作者

    Lu Yi; Liang Mingming; Zhang Quanjun; Liu Zhiquan; Song Yuning; Lai Liangxue; Li Zhanjun;

  • 作者单位

    Jilin Univ Coll Vet Med Inst Zoonosis Minist Educ Key Lab Zoonosis Res Changchun 130062 Jilin;

    Jilin Univ Coll Vet Med Inst Zoonosis Minist Educ Key Lab Zoonosis Res Changchun 130062 Jilin;

    Chinese Acad Sci South China Inst Stem Cell Biol &

    Regenerat Med CAS Key Lab Regenerat Biol;

    Jilin Univ Coll Vet Med Inst Zoonosis Minist Educ Key Lab Zoonosis Res Changchun 130062 Jilin;

    Jilin Univ Coll Vet Med Inst Zoonosis Minist Educ Key Lab Zoonosis Res Changchun 130062 Jilin;

    Jilin Univ Coll Vet Med Inst Zoonosis Minist Educ Key Lab Zoonosis Res Changchun 130062 Jilin;

    Jilin Univ Coll Vet Med Inst Zoonosis Minist Educ Key Lab Zoonosis Res Changchun 130062 Jilin;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    GADD45G; Cleft lip; Rabbit; CRISPR/Cas9; BE4-Gam;

    机译：Gadd45g;唇裂;兔子;CRISPR / CAS9;BE4-GAM;

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