2026年02月03日 星期二

> Tbx6基因编辑小鼠

中文名称Chinese name Tbx6基因编辑小鼠
编号Model number
英文名称English name Tbx6 gene edited mouse
物种Species name 小鼠
品系Strain name
人类疾病Human diseases
传染性Infectivity
微生物Microorganism
类别Category 基因工程动物模型
造模因素Modeling factors 基因敲除/基因敲入
制作方法Making method 采用CRISPR/Cas9技术,在FVB/NJ小鼠上进行基因编辑。首先,在exon2上加入1bp的碱基插入,造成重要T-box区域的移码突变,该移码突变将严重影响Tbx6基因的正常功能,模仿人类遗传学发现的无效突变。研究证实Tbx6纯合突变的小鼠胚胎期致死,这与先前的研究一致。随后,参考人类的亚效等位基因,我们在Tbx6基因的promotor区域进行基因编辑,获得了Tbx6亚效等位基因(Tbx6 mh),并在luciferase实验中证实其基因功能约为野生型Tbx6基因的70%。Tbx6mh/mh 和Tbx6+/-交配即获得TACS小鼠。
生物学特征Biological characteristics microCT及骨骼染色见骨骼畸形
医学用途Medical use
临床表现Clinical manifestation 胸腰段椎体畸形
病理表现Pathology 胚胎期椎体发育不良
发病天数Days of onset
发病过程Pathogenesis process
临床诊断Clinical diagnosis
评价模型成功的指标Indicators for evaluating model success
保藏单位Preservation unit
参考文献Reference 1: Yang N, Wu N, Zhang L, Wu Z, Lupski JR, Zhang F, et al. TBX6 compound inheritance leads to congenital vertebral malformations in humans and mice. Hum Mol Genet. 2019 Feb 15;28(4):539-547. 2: Ren X, Yang N, Wu N, Shi J, Zhang F, Liu P et al. Increased TBX6 gene dosages induce congenital cervical vertebral malformations in humans and mice. J Med Genet. 2020 Jun;57(6):371-379. 3: Liu J, Wu N, Yang N, Lupski JR, Zhang F, Qiu G, et al. TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model. Genet Med. 2019 Jul;21(7):1548-1558. 4: Yang N, Wu N, Dong S, Wu Z, Lupski JR, Zhang F, et al. Human and mouse studies establish TBX6 in Mendelian CAKUT and as a potential driver of kidney defects associated with the 16p11.2 microdeletion syndrome. Kidney Int. 2020 Oct;98(4):1020-1030. 5 Wu N, Ming X, Xiao J, Lupski JR, Qiu G, Zhang F, et al. TBX6 null variants and a common hypomorphic allele in congenital scoliosis. N Engl J Med. 2015 Jan 22;372(4):341-50.
录入/更新时间Date 12-03-20
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