Brent Julie M, Tian Zuozhen, Shofer Frances S, Martin John T, Yao Lutian, Acharte Christian, Chen Youhai H, Qin Ling, Enomoto-Iwamoto Motomi, Zhang Yejia
University Laboratory Animal Resources, University of Pennsylvania, Philadelphia, Pennsylvania;, Email:
Departments of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Comp Med. 2020 Apr 1;70(2):131-139. doi: 10.30802/AALAS-CM-19-000034. Epub 2020 Mar 10.
To facilitate rational experimental design and fulfill the NIH requirement of including sex as a biologic variable, we examined the influences of genetic background and sex on responses to intervertebral disc (IVD) injury in the mouse tail. The goal of this study was to compare gene expression and histologic changes in response to a tail IVD injury (needle puncture) in male and female mice on the DBA and C57BL/6 (B6) backgrounds. We hypothesized that extracellular matrix gene expression in response to IVD injury differs between mice of different genetic backgrounds and sex. Consistent changes were detected in gene expression and histologic features after IVD injury in mice on both genetic backgrounds and sexes. In particular, expression of and was higher in the injured IVD of DBA mice than B6 mice. Conversely, expression was higher in B6 mice than DBA mice. Sex-associated differences were significant only in B6 mice, in which expression was greater in male mice than in female. Histologic differences in response to injury were not apparent between DBA and B6 mice or between males and females. In conclusion, mouse tail IVD showed sex- and strain-related changes in gene expression and histology after needle puncture. The magnitude of change in gene expression differed with regard to genetic background and, to a lesser degree, sex.
为便于进行合理的实验设计并满足美国国立卫生研究院(NIH)将性别作为生物学变量纳入研究的要求,我们研究了遗传背景和性别对小鼠尾部椎间盘(IVD)损伤反应的影响。本研究的目的是比较DBA和C57BL/6(B6)背景的雄性和雌性小鼠在尾部IVD损伤(针刺)后的基因表达和组织学变化。我们假设不同遗传背景和性别的小鼠对IVD损伤的细胞外基质基因表达存在差异。在两种遗传背景和性别的小鼠IVD损伤后,均检测到基因表达和组织学特征的一致变化。特别是,DBA小鼠损伤的IVD中 和 的表达高于B6小鼠。相反,B6小鼠中 的表达高于DBA小鼠。性别相关差异仅在B6小鼠中显著,其中雄性小鼠的 表达高于雌性。DBA和B6小鼠之间或雄性和雌性之间对损伤的组织学差异不明显。总之,小鼠尾部IVD在针刺后显示出基因表达和组织学上与性别和品系相关的变化。基因表达变化的程度因遗传背景而异,在较小程度上也因性别而异。