通过Cre-loxP技术构建<em>GDF11</em>肝脏特异性敲除小鼠模型

doi:10.3969/j.issn.1674-7968.2025.11.015

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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.

Key words： Growth differentiation factor 11 (GDF11) Liver tissue-specific knockout Cre-loxP recombinase system

Received: 20 March 2025

ZTFLH:	S856.2
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Corresponding Authors: ^*jinlianhua@nwsuaf.edu.cn

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	Articles by authors
	ZHANG Zeng-Yu
	LI Ba-Lun
	LING Zi-Xi
	DAI Jian-Qi
	ZHU Wen-Long
	HUA Jin-Lian

Cite this article:

ZHANG Zeng-Yu,LI Ba-Lun,LING Zi-Xi, et al. Generation of a Liver-specific GDF11 Knockout Mouse (Mus musculus)Model via the Cre-loxP System[J]. 农业生物技术学报, 2025, 33(11): 2517-2525.

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https://journal05.magtech.org.cn/Jwk_ny/EN/10.3969/j.issn.1674-7968.2025.11.015 OR https://journal05.magtech.org.cn/Jwk_ny/EN/Y2025/V33/I11/2517

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