Development of the Nude Rabbit Model.

Development of the Nude Rabbit Model.
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DOI:
10.1016/j.stemcr.2021.01.010
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发表时间:
2021-03-09
期刊:
影响因子:
5.9
通讯作者:
Xu J
Xu J
中科院分区:
医学1区
文献类型:
--
作者:
Song J;Hoenerhoff M;Yang D;Yang Y;Deng C;Wen L;Ma L;Pallas B;Zhao C;Koike Y;Koike T;Lester P;Yang B;Zhang J;Chen YE;Xu J

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叉头盒N1 (FOXN1)基因的功能缺失突变导致裸性严重联合免疫缺陷,这是一种罕见的遗传综合征,其特征是胸腺功能不全、严重T细胞免疫缺陷、先天性脱发和指甲营养不良。我们最近利用CRISPR-Cas9技术培育出了FOXN1突变体裸兔(NuRabbits)。在这里,我们报告了nurrabbit殖民地的建立和维持。nurrabbit和裸鼠一样,没有毛,没有胸腺发育,也有免疫缺陷。为了证明nurrabbit在生物医学研究中的功能应用,我们表明它们可以成功地作为人类诱导多能干细胞或组织工程血管异种移植实验的受体动物。我们的工作提出nurrabbit作为免疫缺陷动物模型家族的新成员。nurrabbit相对较大的尺寸和较长的寿命在再生医学、癌症研究和各种其他人类疾病(包括免疫缺陷)的研究中提供了独特的应用。由于FOXN1基因突变,nurrabbit是裸兔和免疫缺陷的。nurrabbit支持iPSC畸胎瘤试验。nurrabbit支持组织工程血管的异种移植。crispr - cas9介导的家兔FOXN1基因敲除导致裸兔(nurrabbit)群体的建立,其特征是裸兔和免疫缺陷表型。nurrabbit支持iPSC畸胎瘤试验和组织工程血管移植。与裸鼠相比,nurrabbit体型更大,寿命更长,在再生医学研究中具有独特的应用机会。
Loss-of-function mutations in the forkhead box N1 (FOXN1) gene lead to nude severe combined immunodeficiency, a rare inherited syndrome characterized by athymia, severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. We recently produced FOXN1 mutant nude rabbits (NuRabbits) by using CRISPR-Cas9. Here we report the establishment and maintenance of the NuRabbit colony. NuRabbits, like nude mice, are hairless, lack thymic development, and are immunodeficient. To demonstrate the functional applications of NuRabbits in biomedical research, we show that they can successfully serve as the recipient animals in xenotransplantation experiments using human induced pluripotent stem cells or tissue-engineered blood vessels. Our work presents the NuRabbit as a new member of the immunodeficient animal model family. The relatively large size and long lifespan of NuRabbits offer unique applications in regenerative medicine, cancer research, and the study of a variety of other human conditions, including immunodeficiency. NuRabbit colony is established and available for the research community NuRabbits are nude and immunodeficient due to a mutation(s) in the FOXN1 gene NuRabbits support iPSC teratoma assay NuRabbits support xenotransplant of tissue-engineered blood vessels CRISPR-Cas9-mediated gene knockout of FOXN1 in rabbits leads to the establishment of the nude rabbit (NuRabbit) colony, characterized by the nude and immunodeficient phenotypes. NuRabbits support iPSC teratoma assay and tissue-engineered blood vessel transplant. The larger size and longer lifespan of NuRabbits, compared with those of nude mice, offer unique application opportunities in regenerative medicine research.
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