一个有缺陷的 Il15 等位基因是导致非肥胖型糖尿病小鼠自然杀伤细胞活性缺陷的原因。
A defective Il15 allele underlies the deficiency in natural killer cell activity in nonobese diabetic mice.
机构信息
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9305-10. doi: 10.1073/pnas.1004492107. Epub 2010 May 3.
Abstract
The nonobese diabetic (NOD) mouse strain has a genetic deficiency in natural killer (NK) cells. This defect underlies this strain's utility in several experimental settings; in particular, it promotes engraftment of human tissue in NOD hosts during the generation of "humanized" mouse models. We have mapped the major NK-cell defect in the NOD vs. C57BL/6 (B6) strain to an inadequately expressed Il15 allele. Treatment of NOD mice with a reagent that specifically enhances interleukin (IL)-15 bioavailability normalized NK-cell numbers and activity in the absence of nonspecific stimulation. These findings raise the possibility of exploiting reagents that impact the IL-15 receptor pathway to facilitate construction of humanized mouse models on non-NOD genetic backgrounds.
摘要
非肥胖型糖尿病（NOD）小鼠品系存在自然杀伤（NK）细胞的遗传缺陷。这种缺陷是该品系在几种实验环境下具有应用价值的基础；特别是，在生成“人源化”小鼠模型时，它促进了人类组织在 NOD 宿主中的移植。我们已经将 NOD 与 C57BL/6（B6）品系相比的主要 NK 细胞缺陷映射到一个表达不足的 Il15 等位基因上。用一种专门增强白细胞介素（IL）-15 生物利用度的试剂处理 NOD 小鼠，可在没有非特异性刺激的情况下使 NK 细胞数量和活性正常化。这些发现提出了利用影响 IL-15 受体途径的试剂来促进在非 NOD 遗传背景上构建人源化小鼠模型的可能性。
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