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敲除内含子嵌套基因可揭示小鼠中相关的T细胞激活功能。

Knocking down , the intron-nested gene, unveils interrelated T cell activation functions in mouse.

作者信息

Ben Khalaf Noureddine, Al-Mashoor Wedad, Saeed Azhar, Raslan Wassim, Bakheit Halla, Abdulhadi Ameera, Marouani Ammar, Taha Safa, Bakhiet Moiz, Fathallah M Dahmani

机构信息

Department of Life Sciences, Health Biotechnology Program, College of Graduates Studies. Arabian Gulf University. Manama, Bahrain.

Department of Pathology, Johns Hopkins Aramco Health Care, Dammam, Saudi Arabia.

出版信息

Biochem Biophys Rep. 2021 Aug 9;27:101100. doi: 10.1016/j.bbrep.2021.101100. eCollection 2021 Sep.

DOI:10.1016/j.bbrep.2021.101100
PMID:34409174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8361231/
Abstract

We previously reported (), a novel gene nested in intron 6 of the mouse gene. is involved in several functions such as fertility and T cell development and its knockout leads to non-viable embryos. We also reported ISRAA's expression in lymphoid organs, particularly in the thymus CD T cells during all developmental stages. In addition, we showed that ISRAA is a binding partner of Fyn and Elf-1 and regulates the expression of T cell activation-related genes . In this paper, we report the generation and characterization of an constitutive knockout mouse. The histological study shows that mice exhibit thymus and spleen hyperplasia. derived T cells showed increased proliferation compared to the wild-type mice T cells. Moreover, gene expression analysis revealed a set of differentially expressed genes in the knockout and wild-type animals during thymus development (mostly genes of T cell activation pathways). Immunological phenotyping of the thymocytes and splenocytes of showed no difference with those of the wild-type. Moreover, we observed that knocking out the intron embedded gene does not affect mice fertility, thus does not disturb this function. The characterization of the mouse confirms the role ISRAA plays in the expression regulation of genes involved in T cell activation established . Taken together, our findings point toward a potential functional interrelation between the intron nested gene and the host gene in regulating T cell activation. This constitutively mice can be a good model to study T cell activation and to investigate the relationship between host and intron-nested genes.

摘要

我们之前报道过(),一个嵌套在小鼠基因内含子6中的新基因。ISRAA参与多种功能,如生育能力和T细胞发育,其敲除会导致胚胎无法存活。我们还报道了ISRAA在淋巴器官中的表达,特别是在胸腺发育的各个阶段的CD T细胞中。此外,我们表明ISRAA是Fyn和Elf-1的结合伙伴,并调节T细胞活化相关基因的表达。在本文中,我们报道了ISRAA组成型敲除小鼠的产生和特征。组织学研究表明,ISRAA敲除小鼠表现出胸腺和脾脏增生。与野生型小鼠T细胞相比,ISRAA敲除小鼠来源的T细胞增殖增加。此外,基因表达分析揭示了在胸腺发育过程中敲除小鼠和野生型动物中一组差异表达的基因(主要是T细胞活化途径的基因)。ISRAA敲除小鼠的胸腺细胞和脾细胞的免疫表型与野生型小鼠没有差异。此外,我们观察到敲除嵌入内含子的基因不会影响小鼠的生育能力,因此不会干扰这一功能。ISRAA敲除小鼠的特征证实了ISRAA在已确定的T细胞活化相关基因表达调控中所起的作用。综上所述,我们的研究结果表明,内含子嵌套基因与宿主基因在调节T细胞活化方面可能存在潜在的功能相互关系。这种组成型ISRAA敲除小鼠可以成为研究T细胞活化以及探究宿主基因与内含子嵌套基因之间关系的良好模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/dc7f757dc37d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/bfed131bbcdb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/608c477af95f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/f0b24f5f7205/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/6834ca779e84/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/202c8d7d61d6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/f1b0d499b480/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/dc7f757dc37d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/bfed131bbcdb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/608c477af95f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/f0b24f5f7205/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/6834ca779e84/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/202c8d7d61d6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/f1b0d499b480/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c909/8361231/dc7f757dc37d/gr7.jpg

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