农业生物技术学报2025，Vol.33Issue(11)：2517-2525,9.DOI:10.3969/j.issn.1674-7968.2025.11.015
通过Cre-loxP技术构建GDF11肝脏特异性敲除小鼠模型
Generation of a Liver-specific GDF11 Knockout Mouse(Mus musculus)Model via the Cre-loxP System
摘要
Abstract
Growth differentiation factor 11(GDF11),as a member of the transforming growth factor β(TGF-β)superfamily,primarily participates in cell growth,differentiation,and tissue regeneration,while also playing a crucial role in embryonic development and the maintenance of adult tissues.To elucidate the role of GDF11 in liver diseases and hepatic aging and to address the deficiency of animal models in liver-related GDF11 research,this study employed the Cre recombinase-loxP site system(Cre-loxP)conditional gene knockout strategy to construct a liver-specific growth differentiation factor 11(GDF11)knockout mouse(Mus musculus)model(C57BL/6J).This model was developed to investigate the regulatory mechanisms of GDF11 in liver aging and overall senescence.Initially,GDF11 gene-edited mice harboring loxP sites GDF11(flox/+)were crossbred with wild-type C57BL/6J mice to generate a substantial population of GDF11(flox/+)heterozygous mice.These were subsequently crossed with Albumin-Cre recombinase(Alb-Cre)transgenic mice,which expressed Cre recombinase specifically in the liver,to produce GDF11(flox/+)Alb-cre(+/-)double transgenic mice.Through intercrossing,a liver-specific GDF11 knockout mouse model was established.Three mice each of GDF11(flox/flox)Alb-cre(+/-),GDF11(flox/+)Alb-cre(+/-),and GDF11(flox/flox)Alb-cre(-/-)genotypes,aged 3～4 weeks,were selected.The efficiency and specificity of gene knockout in the target organ were assessed,and combined RNA and protein level analyses confirmed the successful construction of the liver-specific GDF11 knockout mouse model.GDF11 expression remained unaffected in the heart,spleen,lungs,and kidneys.Quantitative analysis revealed significant differences in GDF11 expression among the groups,and immunohistochemistry and Western blot results indicated a reduction in GDF11 protein levels in liver tissues.The established mouse model provides a robust platform for exploring the physiological and pathological roles of GDF11 in liver aging and systemic senescence.关键词
生长转化因子11(GDF11)/肝脏组织特异性敲除/Cre-loxP重组酶系统Key words
Growth differentiation factor 11(GDF11)/Liver tissue-specific knockout/Cre-loxP recombinase system分类
农业科技引用本文复制引用
张增宇,李巴仑,凌子淅,戴健琪,朱文龙,华进联..通过Cre-loxP技术构建GDF11肝脏特异性敲除小鼠模型[J].农业生物技术学报,2025,33(11):2517-2525,9.基金项目
国家自然科学基金(32372970) （32372970）
国家重点研发计划(2022YFD1302201) （2022YFD1302201）
陕西省农业核心技术攻关和畜牧专项(2024NYGG005-6,20230978) （2024NYGG005-6,20230978）
