An extensive phenotypic characterization of the hTNFalpha transgenic mice.

An extensive phenotypic characterization of the hTNFalpha transgenic mice.
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Htnfalpha转基因小鼠的广泛表型表征。

DOI:
10.1186/1472-6793-7-13
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发表时间:
2007-12-10
期刊:
影响因子:
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通讯作者:
Buiakova, Olesia
Buiakova, Olesia
中科院分区:
其他
文献类型:
--
作者:
Hayward, Michael D;Jones, Beverly K;Saparov, Arman;Hain, Heather S;Trillat, Anne-Cecile;Bunzel, Michelle M;Corona, Aaron;Li-Wang, Bifang;Strenkowski, Bryan;Giordano, Caroline;Shen, Hai;Arcamone, Emily;Weidlick, Jeffrey;Vilensky, Maria;Tugusheva, Marina;Felkner, Roland H;Campbell, William;Rao, Yu;Grass, David S;Buiakova, Olesia

文献摘要

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肿瘤坏死因子α参与多种病理生理过程,包括慢性炎症、冠心病、糖尿病、肥胖和恶病质。表达人肿瘤坏死因子α(hTNFα)的转基因小鼠此前被描述为进行性类风湿性关节炎的模型。在这份报告中,我们描述了一个人肿瘤坏死因子α转基因小鼠品系的广泛特征。除关节炎外,这些h肿瘤坏死因子α转基因小鼠的身体成分、代谢率、瘦素水平、对高脂肪饮食的反应、骨密度和含量、生育能力和男性性功能都发生了重大变化。许多表型在男性中表现出更早的发病和更高的严重程度,表明对肿瘤坏死因子α表达的解除调控导致了显著程度的性二型性。这些结果突出了这种转基因模型作为研究结构性表达的低水平循环肿瘤坏死因子α的进展效应的潜在有用的资源,这种情况类似于在许多人类病理条件下观察到的情况。
Tumor necrosis factor alpha (TNFα) is implicated in a wide variety of pathological and physiological processes, including chronic inflammatory conditions, coronary artery disease, diabetes, obesity, and cachexia. Transgenic mice expressing human TNFα (hTNFα) have previously been described as a model for progressive rheumatoid arthritis. In this report, we describe extensive characterization of an hTNFα transgenic mouse line. In addition to arthritis, these hTNFα transgenic mice demonstrated major alterations in body composition, metabolic rate, leptin levels, response to a high-fat diet, bone mineral density and content, impaired fertility and male sexual function. Many phenotypes displayed an earlier onset and a higher degree of severity in males, pointing towards a significant degree of sexual dimorphism in response to deregulated expression of TNFα. These results highlight the potential usefulness of this transgenic model as a resource for studying the progressive effects of constitutively expressed low levels of circulating TNFα, a condition mimicking that observed in a number of human pathological conditions.