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巢蛋白-Cre介导的条件性敲除小鼠中的性连锁生长障碍与垂体基因表达异常

Sex-Linked Growth Disorder and Aberrant Pituitary Gene Expression in Nestin-Cre-Mediated Conditional Knockout Mice.

作者信息

Swilley Cody, Lin Yu, Zheng Yuze, Xu Xiguang, Liu Min, Zimmerman Kurt, Xie Hehuang

机构信息

Epigenomics and Computational Biology Lab, Fralin Life Sciences Institute of Virginia Tech, Blacksburg, VA 24061, USA.

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.

出版信息

Biology (Basel). 2023 Jul 6;12(7):966. doi: 10.3390/biology12070966.

Abstract

Genes that regulate hormone release are essential for maintaining metabolism and energy balance. encodes a transcription factor that regulates hormone production and release, and a decreased in growth hormones has been reported in knockout mice. A reduction in growth hormones has also been observed in Nestin-Cre mice, a model frequently used to study the nervous system. Currently, it is unknown how loss or the Nestin-Cre driver disrupt pituitary gene expression. Here, we compared the growth curves and pituitary gene expression profiles of Nestin-Cre-mediated conditional knockout (cKO) mice with those of their controls. Reduced body weight was observed in both the Nestin-Cre and cKO mice, and the loss of had a slightly more severe impact on female mice than on male mice. RNA-seq data analyses revealed that the sex-related differences were amplified in the Nestin-Cre-mediated conditional knockout mice. Additionally, in the male mice, the influence of cKO on pituitary gene expression may be overridden by the Nestin-Cre driver. Differentially expressed genes associated with the Nestin-Cre driver were significantly enriched for genes related to growth factor activity and binding. Altogether, our results demonstrate that Nestin-Cre and the loss of in the neuronal cell lineage have distinct impacts on pituitary gene expression in a sex-specific manner.

摘要

调节激素释放的基因对于维持新陈代谢和能量平衡至关重要。[基因名称]编码一种调节激素产生和释放的转录因子,据报道在[基因名称]敲除小鼠中生长激素减少。在常用于研究神经系统的Nestin-Cre小鼠中也观察到生长激素减少。目前,尚不清楚[基因名称]缺失或Nestin-Cre驱动因子如何破坏垂体基因表达。在这里,我们比较了Nestin-Cre介导的[基因名称]条件性敲除(cKO)小鼠与其对照小鼠的生长曲线和垂体基因表达谱。在Nestin-Cre和cKO小鼠中均观察到体重减轻,并且[基因名称]缺失对雌性小鼠的影响比对雄性小鼠的影响略严重。RNA测序数据分析表明,在Nestin-Cre介导的[基因名称]条件性敲除小鼠中,性别相关差异被放大。此外,在雄性小鼠中,cKO对垂体基因表达的影响可能被Nestin-Cre驱动因子所掩盖。与Nestin-Cre驱动因子相关的差异表达基因在与生长因子活性和结合相关的基因中显著富集。总之,我们的结果表明,Nestin-Cre和神经元细胞系中[基因名称]的缺失以性别特异性方式对垂体基因表达有不同影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed0c/10376842/69509afc4c12/biology-12-00966-g001.jpg

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