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生成耐热小鼠模型。

Generating a Heat-Tolerance Mouse Model.

机构信息

Stem Cells and Genome Editing, Genomics and Cellular Sciences, Agriculture Victoria Research, Bundoora, VIC, Australia.

Aquatics & Livestock Sciences, South Australian Research and Development Institute, Roseworthy, SA, Australia.

出版信息

Methods Mol Biol. 2022;2495:259-272. doi: 10.1007/978-1-0716-2301-5_14.

Abstract

Creating mouse models of human genetic disease (Gurumurthy and Lloyd, Dis Models Mech 12(1):dmm029462, 2019) and livestock trait (Schering et al. Arch Physiol Biochem 121(5):194-205, 2015; Habiela et al. J Gen Virol 95 (Pt 11):2329-2345, 2014) have been proven to be a useful tool for understanding the mechanism behind the phenotypes and fundamental and applied research in livestock. A single base pair deletion of prolactin receptor (PRLR) has an impact on hair morphology phenotypes beyond its classical roles in lactation in cattle, the so-called slick cattle (Littlejohn et al. Nat Commun 5:5861, 2014). Here, we generate a knock-in mouse model by targeting the specific locus of PRLR gene using Cas9-mediated genome editing via homology-directed repair (HDR) in mouse zygotes. The mouse model carrying the identical PRLR mutation in slick cattle may provide a useful animal model to study the pathway of thermoregulation and the mechanism of heat-tolerance in the livestock.

摘要

创建人类遗传疾病(Gurumurthy 和 Lloyd,Dis Models Mech 12(1):dmm029462,2019)和家畜性状的小鼠模型(Schering 等人,Arch Physiol Biochem 121(5):194-205,2015;Habiela 等人,J Gen Virol 95 (Pt 11):2329-2345,2014)已被证明是理解表型背后机制的有用工具,以及家畜的基础和应用研究。在牛中,除了其在泌乳中的经典作用外,催乳素受体(PRLR)的单个碱基对缺失对毛发形态表型有影响,即所谓的光滑牛(Littlejohn 等人,Nat Commun 5:5861,2014)。在这里,我们通过在小鼠受精卵中使用 Cas9 介导的基因组编辑通过同源定向修复(HDR)来靶向 PRLR 基因的特定基因座,生成了一种敲入小鼠模型。携带与光滑牛中相同 PRLR 突变的小鼠模型可能为研究家畜的体温调节途径和耐热机制提供有用的动物模型。

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