Severe combined immunodeficiency (SCID) is described as the lack of functional T and B cells. In some cases, mutant genes encoding proteins involved in the process of VDJ recombination retain partial activity and are classified as hypomorphs. Hypomorphic activity in the products from these genes can function in the development of T and B cells and is referred to as a leaky phenotype in patients and animals diagnosed with SCID. We previously described two natural, single nucleotide variants in ARTEMIS (DCLR1EC) in a line of Yorkshire pigs that resulted in SCID. One allele contains a splice site mutation within intron 8 of the ARTEMIS gene (ART16), while the other mutation is within exon 10 that results in a premature stop codon (ART12). While initially characterized as SCID and lacking normal levels of circulating lymphoid cells, low levels of CD3ε+ cells can be detected in most SCID animals. Upon further assessment, we found that ART16/16, and ART12/12 SCID pigs had abnormally small populations of CD3ε+ cells, but not CD79α+ cells, in circulation and lymph nodes. Newborn pigs (0 days of age) had CD3ε+ cells within lymph nodes prior to any environmental exposure. CD3ε+ cells in SCID pigs appeared to have a skewed CD4α+CD8α+CD8β- T helper memory phenotype. Additionally, in some pigs, rearranged VDJ joints were detected in lymph node cells as probed by PCR amplification of TCRδ V5 and J1 genomic loci, as well as TCRβ V20 and J1.1, providing molecular evidence of residual Artemis activity. We additionally confirmed that TCRα and TCRδ constant region transcripts were expressed in the thymic and lymph node tissues of SCID pigs; although the expression pattern was abnormal compared to carrier animals. The leaky phenotype is important to characterize, as SCID pigs are an important tool for biomedical research and this additional phenotype may need to be considered. The pig model also provides a relevant model for hypomorphic human SCID patients.

中文翻译：

---

由于ARTEMIS缺陷而患有严重的联合免疫缺陷的猪CD3ε+细胞。

严重的联合免疫缺陷症（SCID）被描述为缺乏功能性T细胞和B细胞。在某些情况下，编码参与VDJ重组过程中蛋白质的突变基因保留部分活性，并被归类为亚型。这些基因的产物的亚同型活性可以在T细胞和B细胞的发育中起作用，并且在诊断为SCID的患者和动物中被称为渗漏表型。我们之前在约克郡猪的系中描述了SCEMI的ARTEMIS（DCLR1EC）中的两个天然单核苷酸变体。一个等位基因在ARTEMIS基因的内含子8（ART16）内包含一个剪接位点突变，而另一个突变在外显子10内，导致过早的终止密码子（ART12）。最初被定性为SCID并且缺乏正常水平的循环淋巴样细胞，在大多数SCID动物中都可以检测到低水平的CD3ε+细胞。经过进一步评估，我们发现ART16 / 16和ART12 / 12 SCID猪的循环和淋巴结中有异常少量的CD3ε+细胞，但没有CD79α+细胞。新生猪（0日龄）在暴露于任何环境之前均在淋巴结内具有CD3ε+细胞。SCID猪的CD3ε+细胞似乎具有偏斜的CD4α+CD8α+CD8β-T辅助记忆表型。另外，在一些猪中，通过PCR扩增TCRδV5和J1基因组位点以及TCRβV20和J1.1，在淋巴结细胞中检测到重排的VDJ关节，提供了残留Artemis活性的分子证据。我们还证实了SCID猪的胸腺和淋巴结组织中均表达了TCRα和TCRδ恒定区转录本。尽管与携带动物相比表达模式是异常的。泄漏表型对于表征非常重要，因为SCID猪是生物医学研究的重要工具，因此可能需要考虑其他表型。猪模型还为亚型人SCID患者提供了相关模型。