Molecular dissection and testing of PRSS37 function through LC-MS/MS and the generation of a PRSS37 humanized mouse model.
Molecular dissection and testing of PRSS37 function through LC-MS/MS and the generation of a PRSS37 humanized mouse model.
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DOI：
10.1038/s41598-023-37700-1
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发表时间：
2023-07-14
影响因子：
4.6
通讯作者：
Matzuk, Martin M.
中科院分区：
文献类型：
--
作者：
Sutton, Courtney;Nozawa, Kaori;Kent, Katarzyna;Saltzman, Alexander;Leng, Mei;Nagarajan, Sureshbabu;Malovannaya, Anna;Ikawa, Masahito;Garcia, Thomas X.;Matzuk, Martin M.
对男性使用非荷尔蒙的男性避孕药的追求仍然存在。丝氨酸蛋白酶37(PRSS37)是一种精子特异性蛋白，在小鼠体内消融时会使它们不育。在这项研究中，我们试图研究PRSS37缺失的分子后遗症，以更好地了解其分子功能，并确定人类PRSS37是否可以挽救基因敲除(KO)小鼠的不孕表型，从而为药物分子测试提供更合适的模型。为此，我们使用CRISPR-EZ建立了缺失PRSS37完整编码区的小鼠，用原核注射法建立了表达人PRSS37的转基因小鼠，将这些品系杂交产生了人源化小鼠，并对KO和对照组织进行了LC-MS/MS分析，以确定可以将分子功能归因于PRSS37的蛋白质组扰动。我们发现我们新产生的Prss 37 KO小鼠系是不育的，我们的人类转基因拯救了KO小鼠的不育表型，我们的蛋白质组学数据不仅为蛋白质组沿着男性生殖道进化提供了新的见解，而且还证明了受PRSS37丢失显著影响的蛋白质。总之，我们报告了广泛的生物学见解，包括对PRSS37功能的洞察和一种新的避孕评估工具的产生。
The quest for a non-hormonal male contraceptive pill for men still exists. Serine protease 37 (PRSS37) is a sperm-specific protein that when ablated in mice renders them sterile. In this study we sought to examine the molecular sequelae of PRSS37 loss to better understand its molecular function, and to determine whether human PRSS37 could rescue the sterility phenotype of knockout (KO) mice, allowing for a more appropriate model for drug molecule testing. To this end, we used CRISPR-EZ to create mice lacking the entire coding region of Prss37, used pronuclear injection to create transgenic mice expressing human PRSS37, intercrossed these lines to generate humanized mice, and performed LC–MS/MS of KO and control tissues to identify proteomic perturbances that could attribute a molecular function to PRSS37. We found that our newly generated Prss37 KO mouse line is sterile, our human transgene rescues the sterility phenotype of KO mice, and our proteomics data not only yields novel insight into the proteome as it evolves along the male reproductive tract, but also demonstrates the proteins significantly influenced by PRSS37 loss. In summary, we report vast biological insight including insight into PRSS37 function and the generation of a novel tool for contraceptive evaluation.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
64.8
作者：
Harris CR;Millman KJ;van der Walt SJ;Gommers R;Virtanen P;Cournapeau D;Wieser E;Taylor J;Berg S;Smith NJ;Kern R;Picus M;Hoyer S;van Kerkwijk MH;Brett M;Haldane A;Del Río JF;Wiebe M;Peterson P;Gérard-Marchant P;Sheppard K;Reddy T;Weckesser W;Abbasi H;Gohlke C;Oliphant TE
通讯作者：
Oliphant TE
影响因子：
14.9
作者：
Groza, Tudor;Gomez, Federico Lopez;Mashhadi, Hamed Haseli;Munoz-Fuentes, Violeta;Gunes, Osman;Wilson, Robert;Cacheiro, Pilar;Frost, Anthony;Keskivali-Bond, Piia;Vardal, Bora;McCoy, Aaron;Cheng, Tsz Kwan;Santos, Luis;Wells, Sara;Smedley, Damian;Mallon, Ann-Marie;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
4.4
作者：
Fondrie WE;Noble WS
通讯作者：
Noble WS
DOI：
10.1016/j.clnu.2010.03.010
发表时间：
2010-12
期刊：
Clinical nutrition (Edinburgh, Scotland)
影响因子：
--
作者：
Dillon EL;Durham WJ;Urban RJ;Sheffield-Moore M
通讯作者：
Sheffield-Moore M