Expression of Human DNAJ (Heat Shock Protein-40) B3 in Humanized UDP-glucuronosyltransferase 1 Mice.
Expression of Human DNAJ (Heat Shock Protein-40) B3 in Humanized UDP-glucuronosyltransferase 1 Mice.
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DOI：
10.3390/ijms160714997
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发表时间：
2015-07-02
影响因子：
5.6
通讯作者：
Fujiwara R
中科院分区：
文献类型：
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作者：
Mitsugi R;Itoh T;Fujiwara R
人类DNAJB3基因编码一种DNAJ（热休克蛋白40；Hsp40）同系物，B亚家族，成员3伴侣蛋白（DNAJB3），在疾病状态下可以下调，如肥胖患者外周血单核细胞（PBMC）中DNAJB3 mRNA的表达降低。近年来，人们开发了人源化UGT - 1小鼠（hUGT1小鼠），其中引入的人UGT1基因含有编码人DNAJB3的基因。在本研究中，我们分析了人DNAJB3 mRNA在hUGT1小鼠中的表达。在检测的组织中，睾丸中人类DNAJB3 mRNA的表达量最高，而肝脏中表达量最低。我们发现小鼠Dnajb3在hUGT1小鼠中的组织特异性表达模式与人Dnajb3非常相似。我们进一步证明，与对照组小鼠相比，高脂肪饮食喂养的hUGT1小鼠肝脏中人DNAJB3的表达水平显著降低，这表明hUGT1小鼠中人DNAJB3的表达在肥胖等疾病条件下可能受到类似的调节。因此，人源化UGT1小鼠可能有助于研究人DNAJB3在体内的生理作用。
The human DNAJB3 gene encodes a DNAJ (Heat shock protein 40; Hsp40) homolog, subfamily B, member 3 chaperone protein (DNAJB3), which can be down-regulated in disease conditions, as observed in decreased expression of DNAJB3 mRNA in peripheral blood mononuclear cells (PBMC) of obese patients. Recently, humanized UDP-glucuronosyltransferase (UGT) 1 mice (hUGT1 mice) were developed, in which the introduced human UGT1 gene contained a gene encoding human DNAJB3. In the present study, we analyzed the expression of human DNAJB3 mRNA in hUGT1 mice. Among the examined tissues, the testis had the highest expression of human DNAJB3 mRNA, while the lowest expression was observed in the liver. We found that the pattern of tissue-specific expression of mouse Dnajb3 in hUGT1 mice was very similar to that of human DNAJB3. We further demonstrated that the expression of human DNAJB3 in the liver was significantly reduced in high-fat-diet-fed hUGT1 mice compared to the expression level in the control mice, indicating that the expression of human DNAJB3 in hUGT1 mice could be similarly regulated in disease conditions such as obesity. Humanized UGT1 mice might therefore be useful to investigate the physiological role of human DNAJB3 in vivo.