Humanized Rag1-/- γc-/- mice support multilineage hematopoiesis and are susceptible to HIV-1 infection via systemic and vaginal routes.
Humanized Rag1-/- γc-/- mice support multilineage hematopoiesis and are susceptible to HIV-1 infection via systemic and vaginal routes.
复制标题
DOI：
10.1371/journal.pone.0020169
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Akkina SR
中科院分区：
文献类型：
--
作者：
Akkina R;Berges BK;Palmer BE;Remling L;Neff CP;Kuruvilla J;Connick E;Folkvord J;Gagliardi K;Kassu A;Akkina SR
最近引入了几种新的免疫缺陷小鼠模型，包括Rag2−/−γc−/−，NOD/SCID， NOD/SCIDγc−/−和NOD/SCIDβ2m−/−株。将这些小鼠与CD34+人造血干细胞进行移植，可以延长移植时间，实现多系造血，并能够产生针对多种抗原的人类免疫反应。然而，不同的小鼠品系和移植人类细胞的不同方法开始说明品系在移植水平、小鼠寿命持续时间和寿命方面的特异性变化。在这些概念验证研究中，我们评估了Balb/c-Rag1−/−γ−/−菌株在人胎肝来源的CD34+造血细胞上的植入，使用与Balb/c-Rag2−/−γ−/−小鼠有效的相同方案。我们证明这些小鼠可以有效地移植，并显示出人类细胞填充不同淋巴器官的多系人类造血。人类细胞的产生持续超过一年，并注意到人类免疫球蛋白的产生。HIV-1感染可导致慢性病毒血症并导致CD4 T细胞损失。为了模拟主要的性传播病毒，我们通过阴道途径向人源化Rag1−/−γc−/−小鼠感染HIV-1，这也导致慢性病毒血症和辅助性T细胞损失。因此，这些小鼠可以进一步用于在体内研究感染人造血系统的人类病原体。
Several new immunodeficient mouse models for human cell engraftment have recently been introduced that include the Rag2−/−γc−/−, NOD/SCID, NOD/SCIDγc−/− and NOD/SCIDβ2m−/− strains. Transplantation of these mice with CD34+ human hematopoietic stem cells leads to prolonged engraftment, multilineage hematopoiesis and the capacity to generate human immune responses against a variety of antigens. However, the various mouse strains used and different methods of engrafting human cells are beginning to illustrate strain specific variations in engraftment levels, duration and longevity of mouse life span. In these proof-of-concept studies we evaluated the Balb/c-Rag1−/−γ−/− strain for engraftment by human fetal liver derived CD34+ hematopoietic cells using the same protocol found to be effective for Balb/c-Rag2−/−γc−/− mice. We demonstrate that these mice can be efficiently engrafted and show multilineage human hematopoiesis with human cells populating different lymphoid organs. Generation of human cells continues beyond a year and production of human immunoglobulins is noted. Infection with HIV-1 leads to chronic viremia with a resultant CD4 T cell loss. To mimic the predominant sexual viral transmission, we challenged humanized Rag1−/−γc−/− mice with HIV-1 via vaginal route which also resulted in chronic viremia and helper T cell loss. Thus these mice can be further exploited for studying human pathogens that infect the human hematopoietic system in an in vivo setting.
登录
查看更多内容
影响因子：
2.3
作者：
Mazurier, F;Fontanellas, A;de Verneuil, H
通讯作者：
de Verneuil, H
影响因子：
20.3
作者：
Kollet, O;Peled, A;Lapidot, T
通讯作者：
Lapidot, T
影响因子：
56.9
作者：
MCCUNE, JM;NAMIKAWA, R;WEISSMAN, IL
通讯作者：
WEISSMAN, IL
影响因子：
--
作者：
An, Dong Sung;Poon, Betty;Uittenbogaart, Christel H.
通讯作者：
Uittenbogaart, Christel H.
影响因子：
30.3
作者：
Legrand N;Ploss A;Balling R;Becker PD;Borsotti C;Brezillon N;Debarry J;de Jong Y;Deng H;Di Santo JP;Eisenbarth S;Eynon E;Flavell RA;Guzman CA;Huntington ND;Kremsdorf D;Manns MP;Manz MG;Mention JJ;Ott M;Rathinam C;Rice CM;Rongvaux A;Stevens S;Spits H;Strick-Marchand H;Takizawa H;van Lent AU;Wang C;Weijer K;Willinger T;Ziegler P
通讯作者：
Ziegler P