Characterization and Prevention of Hypovitaminosis C in Chimeric Mice with Humanized Livers.

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES
Erin K Touchette, Maria C Bates, Mitch C Johnson, Tracy C O'Brien, Roger J Melton, Kelly R Long, Masakazu Kakuni, Matthew Baginski, Daniel R Radiloff, John E Sagartz
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引用次数: 1

Abstract

Humanized liver chimeric mice (PXB-mice) are generated by the transplantation of human hepatocytes into mice that have severe combined immunodeficiency and express an albumin-promoted urokinase-type plasminogen activator (cDNA-uPA/SCID) transgene. Human hepatocytes cannot synthesize ascorbic acid (AA; commonly called vitamin C) and humans require supplementation to prevent vitamin C deficiency. PXB-mouse livers contain up to approximately 95% human hepatocytes, which likely affects AA synthesis. To determine whether dietary AA supplementation prevents scurvy-like symptoms and death in PXB-mice, a 12 week study that compared nonsupplemented and supplemented PXB-mice was conducted. Approximately 4 weeks into the study, PXB-mice without dietary supplementation of AA displayed weight loss and clinical signs of hypovitaminosis C, including hunched posture, unkempt appearance, and lameness. Pathologic evaluation of nonsupplemented PXB-mice revealed lesions consistent with hypovitaminosis C. Mean serum AA concentrations in the nonsupplemented PXB-mice were below the limit of quantitation (0.5 μg/mL) and were substantially less than those of controls. AA was also measured in a number of tissues, including adrenal gland, brain, liver, and testis; low AA concentrations were similarly observed in tissues obtained from the nonsupplemented PXB-mice. Collectively, these findings support AA supplementation in PXB-mice to prevent the development of hypovitaminosis C and the potential utility of nonsupplemented PXB-mice as an animal model of scurvy.

人源化肝脏嵌合小鼠维生素C缺乏症的特征及预防。
人源化肝嵌合小鼠(pxb -小鼠)是通过将人肝细胞移植到具有严重联合免疫缺陷的小鼠体内,并表达白蛋白促进尿激酶型纤溶酶原激活物(cDNA-uPA/SCID)转基因而产生的。人肝细胞不能合成抗坏血酸(AA);通常称为维生素C),人类需要补充维生素C来预防维生素C缺乏。pxb小鼠肝脏含有大约95%的人肝细胞,这可能影响AA的合成。为了确定膳食补充AA是否能预防pxb小鼠坏血病样症状和死亡,进行了一项为期12周的研究,比较了未补充和补充的pxb小鼠。在研究大约4周后,未补充AA的pxb小鼠表现出体重减轻和维生素缺乏症C的临床症状,包括驼背、外表不整洁和跛行。未补充pxb小鼠的病理评价显示病变与维生素c缺乏症一致。未补充pxb小鼠的平均血清AA浓度低于定量限(0.5 μg/mL),且显著低于对照组。在肾上腺、脑、肝和睾丸等组织中也测量了AA;同样,在未补充pxb小鼠的组织中也观察到低AA浓度。总之,这些发现支持在pxb小鼠中补充AA可以预防维生素缺乏症C的发展,以及未补充pxb小鼠作为坏血病动物模型的潜在效用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Comparative medicine
Comparative medicine 医学-动物学
CiteScore
1.90
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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