Generation of beta-lactoglobulin-modified transgenic goats by homologous recombination

doi:10.1111/febs.13950

NWIPB OpenIR

	Generation of beta-lactoglobulin-modified transgenic goats by homologous recombination
	Zhu, Hongmei 1,2; Hu, Linyong 1,3; Liu, Jun 1,2; Chen, Huatao 1,2; Cui, Chenchen 1,2; Song, Yujie 1,2; Jin, Yaping 1,2; Zhang, Yong 1,2
	2016-12-01
发表期刊	FEBS Journal
卷号	283 期号:24 页码:4600-4613
文章类型	Article
摘要	beta-Lactoglobulin (BLG) is a dominant allergen present in the milk of goats and other ungulates, although it is not found in human breast milk. Thus, the presence of BLG restricts the consumption of goat's milk by humans. In the present study, we examined whether the disruption of the BLG gene in goats by homologous recombination (HR) reduced BLG content in goat's milk and decreased the allergic response to milk. In one approach, exon 2 of the BLG gene was efficiently targeted using HR with a BLG knockout vector. In a second approach to disrupt BLG gene expression and drive exogenous human alpha-lactalbumin (hLA) gene expression, two hLA knock-in constructs were used to target exons 1-4 of the BLG gene via HR, and expression of hLA was then confirmed in goat mammary epithelial cells in vitro. The recombinant clones from both approaches were then used for somatic cell nuclear transfer, generating two transgenic goats possessing a BLG knockout allele or site-specific hLA integration allele. Milk assays demonstrated a reduction in BLG levels in both the BLG knockout and hLA knock-in goats; furthermore, hLA was present in the hLA knock-in goat's milk. Allergenic analysis in mice indicated that the transgenic goat's milk was less allergenic than wild-type goat's milk. These results support the development of gene-targeted animals as an effective tool for reducing allergic reactions to milk and improving nutrition.
关键词	Homologous Recombination Milk Allergy Somatic Cell Nuclear Transfer Transgenic Goat Beta-lactoglobulin
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.1111/febs.13950
关键词[WOS]	MAMMARY EPITHELIAL-CELLS ; ALPHA-LACTALBUMIN ; NUCLEAR TRANSFER ; MAMMALIAN-CELLS ; GENE-EXPRESSION ; COWS MILK ; ALLERGY ; ALLERGENICITY ; LACTATION ; INCREASES
收录类别	SCI
语种	英语
项目资助者	Keystone Project of Transfergene in China(2008ZX08008-004) ; National Natural Science Foundation of China(31302045)
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000392744800015
引用统计	被引频次：8[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/6780
专题	中国科学院西北高原生物研究所
作者单位	1.Northwest A&F Univ, Coll Vet Med, Yangling 712100, Shaanxi, Peoples R China 2.Northwest A&F Univ, Minist Agr, Key Lab Anim Biotechnol, Yangling, Shaanxi, Peoples R China 3.Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Adaptat & Evolut Plateau Biota, Xining, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Hongmei,Hu, Linyong,Liu, Jun,et al. Generation of beta-lactoglobulin-modified transgenic goats by homologous recombination[J]. FEBS Journal,2016,283(24):4600-4613.
APA	Zhu, Hongmei.,Hu, Linyong.,Liu, Jun.,Chen, Huatao.,Cui, Chenchen.,...&Zhang, Yong.(2016).Generation of beta-lactoglobulin-modified transgenic goats by homologous recombination.FEBS Journal,283(24),4600-4613.
MLA	Zhu, Hongmei,et al."Generation of beta-lactoglobulin-modified transgenic goats by homologous recombination".FEBS Journal 283.24(2016):4600-4613.