Generation and characterization of an immunodeficient mouse model of mucopolysaccharidosis type II.
Generation and characterization of an immunodeficient mouse model of mucopolysaccharidosis type II.
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II 型粘多糖贮积症免疫缺陷小鼠模型的生成和表征。
DOI：
10.1016/j.ymgme.2023.107539
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发表时间：
2023-04
影响因子：
3.8
通讯作者：
McIvor, R. Scott
中科院分区：
文献类型：
--
作者：
Smith, Miles C.;Belur, Lalitha R.;Karlen, Andrea D.;Podetz-Pedersen, Kelly;Erlanson, Olivia;Laoharawee, Kanut;Furcich, Justin;Lund, Troy C.;You, Yun;Seelig, Davis;Webber, Beau R.;McIvor, R. Scott
关键词：
粘多糖病II型（Hunter综合征，MPS II）是一种遗传的x连锁隐性疾病，由iduronate-2-sulfatase （IDS）缺乏引起，导致糖胺聚糖（GAG）肝素和皮肤硫酸酯的积累。MPS II小鼠模型已在几篇报道中用于研究疾病病理学并为当前和下一代疗法进行临床前研究。在这里，我们报告了MPS II免疫缺陷小鼠模型的生成和表征，其中使用CRISPR/Cas9敲除NOD/SCID/Il2rγ (NSG)免疫缺陷背景上的部分小鼠IDS基因。IDS−/−NSG小鼠在血浆和所有分析组织中缺乏可检测到的IDS活性，并且在这些组织和尿液中显示出高水平的gag。组织病理学显示NSG-MPS II小鼠外周和中枢神经系统均有空泡化细胞。该模型概括了骨骼疾病的表现，如颧弓直径增加和股骨长度减少。在NSG-MPS II模型中也观察到空间记忆和学习的神经认知缺陷。我们预计这种新的免疫缺陷模型将适用于用于治疗MPS II的人类细胞产品异种移植的临床前研究。
Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an inherited X-linked recessive disease caused by deficiency of iduronate-2-sulfatase (IDS), resulting in the accumulation of the glycosaminoglycans (GAG) heparan and dermatan sulfates. Mouse models of MPS II have been used in several reports to study disease pathology and to conduct preclinical studies for current and next generation therapies. Here, we report the generation and characterization of an immunodeficient mouse model of MPS II, where CRISPR/Cas9 was employed to knock out a portion of the murine IDS gene on the NOD/SCID/Il2rγ (NSG) immunodeficient background. IDS−/− NSG mice lacked detectable IDS activity in plasma and all analyzed tissues and exhibited elevated levels of GAGs in those same tissues and in the urine. Histopathology revealed vacuolized cells in both the periphery and CNS of NSG-MPS II mice. This model recapitulates skeletal disease manifestations, such as increased zygomatic arch diameter and decreased femur length. Neurocognitive deficits in spatial memory and learning were also observed in the NSG-MPS II model. We anticipate that this new immunodeficient model will be appropriate for preclinical studies involving xenotransplantation of human cell products intended for the treatment of MPS II.
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影响因子：
12.4
作者：
Harmatz, Paul;Prada, Carlos E.;Burton, Barbara K.;Lau, Heather;Kessler, Craig M.;Cao, Liching;Falaleeva, Marina;Villegas, Andres G.;Zeitler, Jennifer;Meyer, Kathleen;Miller, Weston;Foo, Cheryl Wong Po;Vaidya, Sagar;Swenson, Wendy;Shiue, Lisa H.;Rouy, Didier;Muenzer, Joseph
通讯作者：
Muenzer, Joseph
影响因子：
5.6
作者：
Hampe CS;Yund BD;Orchard PJ;Lund TC;Wesley J;McIvor RS
通讯作者：
McIvor RS
影响因子：
3.2
作者：
Jangalwe, Sonal;Shultz, Leonard D;Mathew, Anuja;Brehm, Michael A
通讯作者：
Brehm, Michael A
DOI：
10.12717/dr.2019.23.2.079
发表时间：
2019-06-01
期刊：
Development & reproduction
影响因子：
--
作者：
Lee, Ji Yoon;Han, A-Reum;Lee, Dong Ryul
通讯作者：
Lee, Dong Ryul
影响因子：
4.2
作者：
Braun, SE;Pan, D;Whitley, CB
通讯作者：
Whitley, CB